A review of the equine age-related changes in the immune system: Comparisons between human and equine aging, with focus on lung-specific immune-aging

Ageing Research Reviews

Volumn 20, Issue , 2015, Pages 11-23

  Hansen, S ^a   Baptiste, K E ^b   Fjeldborg, J ^a   Horohov, D W ^c  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b Department of Veterinary Medicine Danish Health and Medicines Authority ^*  (Denmark)

^c UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Equine; Immune system; Immunosenescence; Inflamm aging; Lung

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 6; INTERLEUKIN 8; LUNG SURFACTANT; MESSENGER RNA; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 8; TUMOR NECROSIS FACTOR ALPHA; CYTOKINE;

ADAPTIVE IMMUNITY; AGING; ANTIBODY RESPONSE; BODY CONSTITUTION; CD4 CD8 RATIO; CYTOKINE PRODUCTION; DETERIORATION; EQUIDAE; HUMAN; HUMORAL IMMUNITY; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOSENESCENCE; INFECTION SENSITIVITY; INNATE IMMUNITY; LUNG ALVEOLUS MACROPHAGE; LUNG FUNCTION; LUNG LAVAGE; MACROPHAGE; NEUTROPHIL; NONHUMAN; OXIDATIVE STRESS; PROTEIN EXPRESSION; RESPIRATORY TRACT INFLAMMATION; REVIEW; SENESCENCE; T LYMPHOCYTE; VACCINATION; ADVERSE EFFECTS; ANIMAL; ANTIBODY SPECIFICITY; BLOOD; ENVIRONMENTAL EXPOSURE; HORSE; IMMUNITY; IMMUNOLOGY; LUNG; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY;

EQUIDAE;

AGING; ANIMALS; CYTOKINES; ENVIRONMENTAL EXPOSURE; HORSES; HUMANS; IMMUNE SYSTEM; IMMUNITY; LUNG; ORGAN SPECIFICITY; OXIDATIVE STRESS; T-LYMPHOCYTES;

EID: 84921416683     PISSN: 15681637     EISSN: 18729649     Source Type: Journal    
DOI: 10.1016/j.arr.2014.12.002     Document Type: Review

References (190)

1. Adams D.O., Hamilton T.A. The cell biology of macrophage activation. Annual Review of Immunology 1984, 2:283-318.
2. Adams A.A., Breathnach C.C., Katepalli M.P., Kohler K., Horohov D.W. Advanced age in horses affects divisional history of T cells and inflammatory cytokine production. Mechanisms of Ageing and Development 2008, 129:656-664.
3. Adams A.A., Katepalli M.P., Kohler K., Reedy S.E., Stilz J.P., Vick M.M., Fitzgerald B.P., Lawrence L.M., Horohov D.W. Effect of body condition, body weight and adiposity on inflammatory cytokine responses in old horses. Veterinary Immunology and Immunopathology 2009, 127:286-294.
4. Adams A.A., Sturgill T.L., Breathnach C.C., Chambers T.M., Siger L., Minke J.M., Horohov D.W. Humoral and cell-mediated immune responses of old horses following recombinant canarypox virus vaccination and subsequent challenge infection. Veterinary Immunology and Immunopathology 2011, 139:128-140.
5. Aguilera-Tejero E., Estepa J.C., Lopez I., Mayer-Valor R., Rodriguez M. Arterial blood gases and acid-base balance in healthy young and aged horses. Equine Veterinary Journal 1998, 30:352-354.
6. Alvarez E., Machado A., Sobrino F., Santa Maria C. Nitric oxide and superoxide anion production decrease with age in resident and activated rat peritoneal macrophages. Cellular Immunology 1996, 169:152-155.
7. Anon USDA/APHIS Part 1: Baseline reference of equine health and management, 2005 2005, 1-60. National Animal Health Monitoring System, Fort Collins, CO, USA.
8. Aoshiba K., Nagai A. Chronic lung inflammation in aging mice. FEBS Letters 2007, 581:3512-3516.
9. Argyle D., Ellsmore V., Gault E.A., Munro A.F., Nasir L. Equine telomeres and telomerase in cellular immortalisation and ageing. Mechanisms of Ageing and Development 2003, 124:759-764.
10. Austin S.M., Foreman J.H., Hungerford L.L. Case-control study of risk factors for development of pleuropneumonia in horses. Journal of the American Veterinary Medical Association 1995, 207:325-328.
11. Balson G.A., Smith G.D., Yager J.A. Immunophenotypic analysis of foal bronchoalveolar lavage lymphocytes. Veterinary Microbiology 1997, 56:237-246.
12. Beekman L., Tohver T., Leguillette R. Comparison of cytokine mRNA expression in the bronchoalveolar lavage fluid of horses with inflammatory airway disease and bronchoalveolar lavage mastocytosis or neutrophilia using REST software analysis. Journal of Veterinary Internal Medicine/American College of Veterinary Internal Medicine 2012, 26:153-161.
13. Beharka A.A., Gaynor C.D., Kang B.K., Voelker D.R., McCormack F.X., Schlesinger L.S. Pulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor expressed on human macrophages. Journal of Immunology 2002, 169:3565-3573.
14. Bellocq A., Azoulay E., Marullo S., Flahault A., Fouqueray B., Philippe C., Cadranel J., Baud L. Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms. American Journal of Respiratory Cell and Molecular Biology 1999, 21:128-136.
15. Berndt A., Derksen F.J., Venta P.J., Ewart S., Yuzbasiyan-Gurkan V., Robinson N.E. Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction. American Journal of Physiology Lung Cellular and Molecular Physiology 2007, 292:L936-L943.
16. Boehmer E.D., Goral J., Faunce D.E., Kovacs E.J. Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression. Journal of Leukocyte Biology 2004, 75:342-349.
17. Boehmer E.D., Meehan M.J., Cutro B.T., Kovacs E.J. Aging negatively skews macrophage TLR2- and TLR4-mediated pro-inflammatory responses without affecting the IL-2-stimulated pathway. Mechanisms of Ageing and Development 2005, 126:1305-1313.
18. Bonafe M., Olivieri F., Cavallone L., Giovagnetti S., Mayegiani F., Cardelli M., Pieri C., Marra M., Antonicelli R., Lisa R., Rizzo M.R., Paolisso G., Monti D., Franceschi C. A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. European Journal of Immunology 2001, 31:2357-2361.
19. Bowler R.P. Surfactant protein D as a biomarker for chronic obstructive pulmonary disease. COPD 2012, 9:651-653.
20. Bruunsgaard H., Andersen-Ranberg K., Hjelmborg J.B., Pedersen B.K., Jeune B. Elevated levels of tumor necrosis factor alpha and mortality in centenarians. The American Journal of Medicine 2003, 115:278-283.
21. Bruunsgaard H., Andersen-Ranberg K., Jeune B., Pedersen A.N., Skinhoj P., Pedersen B.K. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 1999, 54:M357-M364.
22. Bruunsgaard H., Pedersen A.N., Schroll M., Skinhoj P., Pedersen B.K. Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans. Clinical and Experimental Immunology 1999, 118:235-241.
23. Bruunsgaard H., Pedersen B.K. Age-related inflammatory cytokines and disease. Immunology and Allergy Clinics of North America 2003, 23:15-39.
24. Bureau F., Delhalle S., Bonizzi G., Fievez L., Dogne S., Kirschvink N., Vanderplasschen A., Merville M.P., Bours V., Lekeux P. Mechanisms of persistent NF-kappa B activity in the bronchi of an animal model of asthma. Journal of Immunology 2000, 165:5822-5830.
25. Cakman I., Rohwer J., Schutz R.M., Kirchner H., Rink L. Dysregulation between TH1 and TH2 T cell subpopulations in the elderly. Mechanisms of Ageing and Development 1996, 87:197-209.
26. Cerveri I., Zoia M.C., Fanfulla F., Spagnolatti L., Berrayah L., Grassi M., Tinelli C. Reference values of arterial oxygen tension in the middle-aged and elderly. American Journal of Respiratory and Critical Care Medicine 1995, 152:934-941.
27. Charron C.E., Chou P.C., Coutts D.J., Kumar V., To M., Akashi K., Pinhu L., Griffiths M., Adcock I.M., Barnes P.J., Ito K. Hypoxia-inducible factor 1alpha induces corticosteroid-insensitive inflammation via reduction of histone deacetylase-2 transcription. The Journal of Biological Chemistry 2009, 284:36047-36054.
28. Chelvarajan R.L., Collins S.M., Van Willigen J.M., Bondada S. The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function. Journal of Leukocyte Biology 2005, 77:503-512.
29. Chesters P.M., Hughes A., Edington N. Equid herpesvirus 1: platelets and alveolar macrophages are potential sources of activated TGF-B1 in the horse. Veterinary Immunology and Immunopathology 2000, 75:71-79.
30. Chiu B.C., Stolberg V.R., Zhang H., Chensue S.W. Increased Foxp3(+) Treg cell activity reduces dendritic cell co-stimulatory molecule expression in aged mice. Mechanisms of Ageing and Development 2007, 128:618-627.
31. Christmann U., Hite R.D., Witonsky S.G., Elvinger F., Werre S.R., Thatcher C.D., Tan R.H., Buechner-Maxwell V.A. Influence of age on surfactant isolated from healthy horses maintained on pasture. Journal of Veterinary Internal Medicine/American College of Veterinary Internal Medicine 2009, 23:612-618.
32. Christmann U., Livesey L.C., Taintor J.S., Waldridge B.M., Schumacher J., Grier B.L., Hite R.D. Lung surfactant function and composition in neonatal foals and adult horses. Journal of Veterinary Internal Medicine/American College of Veterinary Internal Medicine 2006, 20:1402-1407.
33. Christmann U., Welles E.G., Waldridge B.M., Schumacher J., Grier B.L., Hite R.D. Abnormalities in lung surfactant in horses clinically affected with recurrent airway obstruction (RAO). Journal of Veterinary Internal Medicine/American College of Veterinary Internal Medicine 2008, 22:1452-1455.
34. Christmann U.D., Hite R.D.M., Tan R.H.H.D., Thatcher C.D.D., Witonsky S.G.D., Werre S.R.P., Buechner-Maxwell V.A.D. Surfactant alterations in horses with recurrent airway obstruction at various clinical stages. AJVR 2010, 71:468-475.
35. Davis M.S., Malayer J.R., Vandeventer L., Royer C.M., McKenzie E.C., Williamson K.K. Cold weather exercise and airway cytokine expression. Journal of Applied Physiology 2005, 98:2132-2136.
36. Deaton C.M. The role of oxidative stress in an equine model of human asthma. Redox Report: Communications in Free Radical Research 2006, 11:46-52.
37. Deaton C.M., Marlin D.J., Roberts C.A., Smith N., Harris P.A., Kelly F.J., Schroter R.C. Antioxidant supplementation and pulmonary function at rest and exercise. Equine Veterinary Journal. Supplement 2002, 58-65.
38. Deaton C.M., Marlin D.J., Smith N.C., Harris P.A., Roberts C.A., Schroter R.C., Kelly F.J. Pulmonary epithelial lining fluid and plasma ascorbic acid concentrations in horses affected by recurrent airway obstruction. AJVR 2004, 65:80-87.
39. Deaton C.M., Marlin D.J., Smith N.C., Smith K.C., Newton R.J., Gower S.M., Cade S.M., Roberts C.A., Harris P.A., Schroter R.C., Kelly F.J. Breath condensate hydrogen peroxide correlates with both airway cytology and epithelial lining fluid ascorbic acid concentration in the horse. Free Radical Research 2004, 38:201-208.
40. De la Fuente M., Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Current Pharmaceutical Design 2009, 15:3003-3026.
41. Der G., Batty G.D., Benzeval M., Deary I.J., Green M.J., McGlynn L., McIntyre A., Robertson T., Shiels P.G. Is telomere length a biomarker for aging: cross-sectional evidence from the west of Scotland?. PLoS ONE 2012, 7:e45166.
42. Desjardins I., Theoret C., Joubert P., Wagner B., Lavoie J.P. Comparison of TGF-beta 1 concentrations in bronchoalveolar fluid of horses affected with heaves and of normal controls. Veterinary Immunology and Immunopathology 2004, 101:133-141.
43. Dinarello C.A. Proinflammatory cytokines. Chest 2000, 118:503-508.
44. Dixon P.M. Respiratory mucociliary clearance in the horse in health and disease, and its pharmaceutical modification. The Veterinary Record 1992, 131:229-235.
45. Effros R.B., Cai Z., Linton P.J. CD8 T cells and aging. Critical Reviews in Immunology 2003, 23:45-64.
46. Elenkov I.J. Glucocorticoids and the Th1/Th2 balance. Annals of the New York Academy of Sciences 2004, 1024:138-146.
47. Elias J.A., Schreiber A.D., Gustilo K., Chien P., Rossman M.D., Lammie P.J., Daniele R.P. Differential interleukin 1 elaboration by unfractionated and density fractionated human alveolar macrophages and blood monocytes: relationship to cell maturity. Journal of Immunology 1985, 135:3198-3204.
48. Fagiolo U., Cossarizza A., Scala E., Fanales-Belasio E., Ortolani C., Cozzi E., Monti D., Franceschi C., Paganelli R. Increased cytokine production in mononuclear cells of healthy elderly people. European Journal of Immunology 1993, 23:2375-2378.
49. Fainaru O., Woolf E., Lotem J., Yarmus M., Brenner O., Goldenberg D., Negreanu V., Bernstein Y., Levanon D., Jung S., Groner Y. Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation. The EMBO Journal 2004, 23:969-979.
50. Fallarino F., Grohmann U., Hwang K.W., Orabona C., Vacca C., Bianchi R., Belladonna M.L., Fioretti M.C., Alegre M.L., Puccetti P. Modulation of tryptophan catabolism by regulatory T cells. Nature Immunology 2003, 4:1206-1212.
51. Fernandez S., Jose P., Avdiushko M.G., Kaplan A.M., Cohen D.A. Inhibition of IL-10 Receptor Function in Alveolar Macrophages by Toll-like Receptor Agonists. Journal of Immunology 2004, 172:2613-2620.
52. Fietta A., Merlini C., De Bernardi P.M., Gandola L., Piccioni P.D., Grassi C. Non specific immunity in aged healthy subjects and in patients with chronic bronchitis. Aging (Milano) 1993, 5:357-361.
53. Flurkey K., Stadecker M., Miller R.A. Memory T lymphocyte hyporesponsiveness to non-cognate stimuli: a key factor in age-related immunodeficiency. European Journal of Immunology 1992, 22:931-935.
54. Franceschi C., Bonafe M., Valensin S., Olivieri F., De Luca M., Ottaviani E., De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Annals of the New York Academy of Sciences 2000, 908:244-254.
55. Franchini M., Gilli U., Akens M.K., Fellenberg R.V., Bracher V. The role of neutrophil chemotactic cytokines in the pathogenesis of equine chronic obstructive pulmonary disease (COPD). Veterinary Immunology and Immunopathology 1998, 66:53-65.
56. Fulop T., Foris G., Worum I., Leovey A. Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes. Clinical and Experimental Immunology 1985, 61:425-432.
57. Fulop T., Fouquet C., Allaire P., Perrin N., Lacombe G., Stankova J., Rola-Pleszczynski M., Gagne D., Wagner J.R., Khalil A., Dupuis G. Changes in apoptosis of human polymorphonuclear granulocytes with aging. Mechanisms of Ageing and Development 1997, 96:15-34.
58. Fulop T., Larbi A., Douziech N., Fortin C., Guerard K.P., Lesur O., Khalil A., Dupuis G. Signal transduction and functional changes in neutrophils with aging. Aging Cell 2004, 3:217-226.
59. Gerber V., Robinson N.E., Luethi S., Marti E., Wampfler B., Straub R. Airway inflammation and mucus in two age groups of asymptomatic well-performing sport horses. Equine Veterinary Journal 2003, 35:491-495.
60. Ghio A.J., Mazan M.R., Hoffman A.M., Robinson N.E. Correlates between human lung injury after particle exposure and recurrent airway obstruction in the horse. Equine Veterinary Journal 2006, 38:362-367.
61. Globerson A. T lymphocytes and aging. International Archives of Allergy and Immunology 1995, 107:491-497.
62. Gomez C.R., Boehmer E.D., Kovacs E.J. The aging innate immune system. Current Opinion in Immunology 2005, 17:457-462.
63. Goto H., Shimizu K., Taya Y., Noda H., Tokunaga T. Antibody responses of horses to equine influenza viruses during a postepizootic period in Japan. Canadian Journal of Comparative Medicine. Revue Canadienne de Medecine Comparee 1982, 46:27-32.
64. Goto H., Yamamoto Y., Ohta C., Shirahata T., Higuchi T., Ohishi H. Antibody responses of Japanese horses to influenza viruses in the past few years. The Journal of Veterinary Medical Science/The Japanese Society of Veterinary Science 1993, 55:33-37.
65. Gregg R., Smith C.M., Clark F.J., Dunnion D., Khan N., Chakraverty R., Nayak L., Moss P.A. The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age. Clinical and Experimental Immunology 2005, 140:540-546.
66. Guirnalda P.D., Malinowski K., Roegner V., Horohov D.W. Effects of age and recombinant equine somatotropin (eST) administration on immune function in female horses. Journal of Animal Science 2001, 79:2651-2658.
67. Haczku A., Cao Y., Vass G., Kierstein S., Nath P., Atochina-Vasserman E.N., Scanlon S.T., Li L., Griswold D.E., Chung K.F., Poulain F.R., Hawgood S., Beers M.F., Crouch E.C. IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. Journal of Immunology 2006, 176:3557-3565.
68. Hansen S., Baptiste K.E., Fjeldborg J., Betancourt A., Horohov D.W. A comparison of pro-inflammatory cytokine mRNA expression in equine bronchoalveolar lavage (BAL) and peripheral blood. Veterinary Immunology and Immunopathology 2014, 158:238-243.
69. Hansen S., Sun L., Baptiste K.E., Fjeldborg J., Horohov D.W. Age-related changes in intracellular expression of IFN-gamma and TNF-alpha in equine lymphocytes measured in bronchoalveolar lavage and peripheral blood. Developmental and Comparative Immunology 2013, 39:228-233.
70. Harman D. Aging: a theory based on free radical and radiation chemistry. Journal of Gerontology 1956, 11:298-300.
71. Harman D. Free radical theory of aging: an update: increasing the functional life span. Annals of the New York Academy of Sciences 2006, 1067:10-21.
72. Harris T.B., Ferrucci L., Tracy R.P., Corti M.C., Wacholder S., Ettinger W.H., Heimovitz H., Cohen H.J., Wallace R. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. The American Journal of Medicine 1999, 106:506-512.
73. Hayashi T., Beck L., Rossetto C., Gong X., Takikawa O., Takabayashi K., Broide D.H., Carson D.A., Raz E. Inhibition of experimental asthma by indoleamine 2,3-dioxygenase. The Journal of Clinical Investigation 2004, 114:270-279.
74. Heller M.C., Drew C.P., Jackson K.A., Griffey S., Watson J.L. A potential role for indoleamine 2,3-dioxygenase (IDO) in Rhodococcus equi infection. Veterinary Immunology and Immunopathology 2010, 138:174-182.
75. Henning L.N., Azad A.K., Parsa K.V., Crowther J.E., Tridandapani S., Schlesinger L.S. Pulmonary surfactant protein A regulates TLR expression and activity in human macrophages. Journal of Immunology 2008, 180:7847-7858.
76. 2) in horses related to age, sex and usage. Veterinary Research Communications 2002, 26:467-478.
77. Herszberg B., Ramos-Barbon D., Tamaoka M., Martin J.G., Lavoie J.P. Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling. The Journal of Allergy and Clinical Immunology 2006, 118:382-388.
78. Ho A.S., Moore K.W. Interleukin-10 and its receptor. Therapeutic Immunology 1994, 1:173-185.
79. Ho J.C., Chan K.N., Hu W.H., Lam W.K., Zheng L., Tipoe G.L., Sun J., Leung R., Tsang K.W. The effect of aging on nasal mucociliary clearance, beat frequency, and ultrastructure of respiratory cilia. American Journal of Respiratory Critical Care Medicine 2001, 163:983-988.
80. Hobo S., Oikawa M., Kuwano A., Yoshida K., Yoshihara T. Effect of transportation on the composition of bronchoalveolar lavage fluid obtained from horses. American Journal of Veterinary Research 1997, 58:531-534.
81. Hobo S., Yoshihara T., Oikawa M., Jones J.H. Surfactant proteins in bronchoalveolar lavage fluid of horses: assay technique and changes following road transport. The Veterinary Record 2001, 148:74-80.
82. Hoffman A.M. Bronchoalveolar lavage: sampling technique and guidelines for cytologic preparation and interpretation. The Veterinary Clinics of North America Equine Practice 2008, 24:423-435. vii-viii.
83. Holt P.G. Inhibitory activity of unstimulated alveolar macrophages on T-lymphocyte blastogenic response. The American Review of Respiratory Disease 1978, 118:791-793.
84. Holt P.G., Oliver J., Bilyk N., McMenamin C., McMenamin P.G., Kraal G., Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. The Journal of Experimental Medicine 1993, 177:397-407.
85. Horohov D., Dimock A., Guirnalda P., Folsom R.W., McKeever K.H., Malinowski K. Effect of exercise on the immune response of young and old horses. AJVR 1999, 60:643-647.
86. Horohov D.W., Adams A.A., Chambers T.M. Immunosenescence of the equine immune system. Journal of Comparative Pathology 2010, 142(Suppl 1):S78L 84.
87. Horohov D.W., Kydd J.H., Hannant D. The effect of aging on T cell responses in the horse. Developmental and Comparative Immunology 2002, 26:121-128.
88. Hotchkiss J.W., Reid S.W., Christley R.M. A survey of horse owners in Great Britain regarding horses in their care. Part 1: Horse demographic characteristics and management. Equine Veterinary Journal 2007, 39:294-300.
89. Hotchkiss J.W., Reid S.W., Christley R.M. A survey of horse owners in Great Britain regarding horses in their care. Part 2: Risk factors for recurrent airway obstruction. Equine Veterinary Journal 2007, 39:301-308.
90. Huang Y.P., Pechere J.C., Michel M., Gauthey L., Loreto M., Curran J.A., Michel J.P. In vivo T cell activation, in vitro defective IL-2 secretion, and response to influenza vaccination in elderly women. Journal of Immunology 1992, 148:715-722.
91. Hunninghake G.W. Immunoregulatory functions of human alveolar macrophages. The American Review of Respiratory Disease 1987, 136:253-254.
92. Ireland J.L., Clegg P.D., McGowan C.M., McKane S.A., Pinchbeck G.L. A cross-sectional study of geriatric horses in the United Kingdom. Part 1: Demographics and management practices. Equine Veterinary Journal 2011, 43:30-36.
93. Ito S., Hobo S., Kasashima Y. Bronchoalveolar lavage fluid findings in the atelectatic regions of anesthetized horses. The Journal of Veterinary Medical Science/The Japanese Society of Veterinary Science 2003, 65:1011-1013.
94. Jost U., Klukowska-Rotzler J., Dolf G., Swinburne J.E., Ramseyer A., Bugno M., Burger D., Blott S., Gerber V. A region on equine chromosome 13 is linked to recurrent airway obstruction in horses. Equine Veterinary Journal 2007, 39:236-241.
95. Kaminski N., Allard J.D., Pittet J.F., Zuo F., Griffiths M.J., Morris D., Huang X., Sheppard D., Heller R.A. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proceedings of the National Academy of Sciences of the United States of America 2000, 97:1778-1783.
96. Karagianni A.E., Kapetanovic R., McGorum B.C., Hume D.A., Pirie S.R. The equine alveolar macrophage: functional and phenotypic comparisons with peritoneal macrophages. Veterinary Immunology and Immunopathology 2013, 155:219-228.
97. Kasper M., Sims G., Koslowski R., Kuss H., Thuemmler M., Fehrenbach H., Auten R.L. Increased surfactant protein D in rat airway goblet and Clara cells during ovalbumin-induced allergic airway inflammation. Clinical and Experimental Allergy 2002, 32:1251-1258.
98. Katepalli M.P., Adams A.A., Lear T.L., Horohov D.W. The effect of age and telomere length on immune function in the horse. Developmental and Comparative Immunology 2008, 32:1409-1415.
99. Kelley J., Shull S., Walsh J.J., Cutroneo K.R., Absher M. Auto-induction of transforming growth factor-beta in human lung fibroblasts. American Journal of Respiratory Cell and Molecular Biology 1993, 8:417-424.
100. Kelly F.J., Mudway I., Krishna M.T., Holgate S.T. The free radical basis of air pollution: focus on ozone. Respiratory Medicine 1995, 89:647-656.
101. Klier J., May A., Fuchs S., Schillinger U., Plank C., Winter G., Gehlen H., Coester C. Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles. Veterinary Immunology and Immunopathology 2011, 144:79-87.
102. Krabbe K.S., Pedersen M., Bruunsgaard H. Inflammatory mediators in the elderly. Experimental Gerontology 2004, 39:687-699.
103. Kuronuma K., Sano H., Kato K., Kudo K., Hyakushima N., Yokota S., Takahashi H., Fujii N., Suzuki H., Kodama T., Abe S., Kuroki Y. Pulmonary surfactant protein A augments the phagocytosis of Streptococcus pneumoniae by alveolar macrophages through a casein kinase 2-dependent increase of cell surface localization of scavenger receptor A. The Journal of Biological Chemistry 2004, 279:21421-21430.
104. Lages C.S., Suffia I., Velilla P.A., Huang B., Warshaw G., Hildeman D.A., Belkaid Y., Chougnet C. Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. Journal of Immunology 2008, 181:1835-1848.
105. Lambrecht B.N. Alveolar macrophage in the driver's seat. Immunity 2006, 24:366-368.
106. Leclere M., Lavoie-Lamoureux A., Lavoie J.P. Heaves, an asthma-like disease of horses. Respirology 2011, 16:1027-1046.
107. Lee J., Sandford A., Man P., Sin D.D. Is the aging process accelerated in chronic obstructive pulmonary disease?. Current Opinion in Pulmonary Medicine 2011, 17:90-97.
108. Letterio J.J., Roberts A.B. Regulation of immune responses by TGF-beta. Annual Review of Immunology 1998, 16:137-161.
109. Lewis D.B., Wilson C.B. Gamma-interferon: an immunoregulatory lymphokine with immunotherapeutic potential. The Pediatric Infectious Disease Journal 1990, 9:642-651.
110. Li Z., Li J., Bu X., Liu X., Tankersley C.G., Wang C., Huang K. Age-induced augmentation of p38 MAPK phosphorylation in mouse lung. Experimental Gerontology 2011, 46:694-702.
111. Liu B., Carle K.W., Whisler R.L. Reductions in the activation of ERK and JNK are associated with decreased IL-2 production in T cells from elderly humans stimulated by the TCR/CD3 complex and costimulatory signals. Cellular Immunology 1997, 182:79-88.
112. Liu C.F., Rivere M., Huang H.J., Puzo G., Wang J.Y. Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expression. Clinical and Experimental Allergy 2010, 40:111-122.
113. Lunn D.P., Holmes M.A., Duffus W.P. Equine T-lymphocyte MHC II expression: variation with age and subset. Veterinary Immunology and Immunopathology 1993, 35:225-238.
114. Malinowski K., Christensen R.A., Konopka A., Scanes C.G., Hafs H.D. Feed intake, body weight, body condition score, musculation, and immunocompetence in aged mares given equine somatotropin. Journal of Animal Science 1997, 75:755-760.
115. Marti E., Gerber H., Essich G., Oulehla J., Lazary S. The genetic basis of equine allergic diseases. 1. Chronic hypersensitivity bronchitis. Equine Veterinary Journal 1991, 23:457-460.
116. Martin C.J., Chihara S., Chang D.B. A comparative study of the mechanical properties in aging alveolar wall. The American Review of Respiratory Disease 1977, 115:981-988.
117. Mauderly J.L., Hahn F.F. The effects of age on lung function and structure of adult animals. Advances in Veterinary Science and Comparative Medicine 1982, 26:35-77.
118. McFarlane D., Sellon D.C., Gaffney D., Hedgpeth V., Papich M., Gibbs S. Hematologic and serum biochemical variables and plasma corticotropin concentration in healthy aged horses. American Journal of Veterinary Research 1998, 59:1247-1251.
119. McFarlane D., Sellon D.C., Gibbs S.A. Age-related quantitative alterations in lymphocyte subsets and immunoglobulin isotypes in healthy horses. American Journal of Veterinary Research 2001, 62:1413-1417.
120. McGorum B.C., Dixon P.M., Halliwell R.E. Phenotypic analysis of peripheral blood and bronchoalveolar lavage fluid lymphocytes in control and chronic obstructive pulmonary disease affected horses, before and after 'natural (hay and straw) challenges'. Veterinary Immunology and Immunopathology 1993, 36:207-222.
121. McKane S.A., Canfield P.J., Rose R.J. Equine bronchoalveolar lavage cytology: survey of thoroughbred racehorses in training. Australian Veterinary Journal 1993, 70:401-404.
122. McKenna R.W., Washington L.T., Aquino D.B., Picker L.J., Kroft S.H. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood 2001, 98:2498-2507.
123. McNerlan S.E., Rea I.M., Alexander H.D., Morris T.C. Changes in natural killer cells, the CD57CD8 subset, and related cytokines in healthy aging. Journal of clinical immunology 1998, 18:31-38.
124. Meyer K.C., Cardoni A., Xiang Z.Z. Vascular endothelial growth factor in bronchoalveolar lavage from normal subjects and patients with diffuse parenchymal lung disease. The Journal of Laboratory and Clinical Medicine 2000, 135:332-338.
125. Meyer K.C., Ershler W., Rosenthal N.S., Lu X.G., Peterson K. Immune dysregulation in the aging human lung. American Journal of Respiratory and Critical Care Medicine 1996, 153:1072-1079.
126. Meyer K.C., Rosenthal N.S., Soergel P., Peterson K. Neutrophils and low-grade inflammation in the seemingly normal aging human lung. Mechanisms of Ageing and Development 1998, 104:169-181.
127. Meyer K.C., Soergel P. Variation of bronchoalveolar lymphocyte phenotypes with age in the physiologically normal human lung. Thorax 1999, 54:697-700.
128. Morris D.G., Huang X., Kaminski N., Wang Y., Shapiro S.D., Dolganov G., Glick A., Sheppard D. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Nature 2003, 422:169-173.
129. Morrison K.E., Slocombe R.F., McKane S.A., Dargaville P.A. Functional and compositional changes in pulmonary surfactant in response to exercise. Equine Veterinary Journal. Supplement 1999, 30:62-66.
130. Mosmann T.R. Properties and functions of interleukin-10. Advances in Immunology 1994, 56:1-26.
131. Mui T.S., Man J.M., McElhaney J.E., Sandford A.J., Coxson H.O., Birmingham C.L., Li Y., Man S.F., Sin D.D. Telomere length and chronic obstructive pulmonary disease: evidence of accelerated aging. Journal of the American Geriatrics Society 2009, 57:2372-2374.
132. Muirhead T.L., McClure J.T., Wichtel J.J., Stryhn H., Markham R.J., McFarlane D., Lunn D.P. The effect of age on the immune response of horses to vaccination. Journal of Comparative Pathology 2010, 142(Suppl 1):S85L 90.
133. Munger J.S., Huang X., Kawakatsu H., Griffiths M.J., Dalton S.L., Wu J., Pittet J.F., Kaminski N., Garat C., Matthay M.A., Rifkin D.B., Sheppard D. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999, 96:319-328.
134. Munn D.H., Shafizadeh E., Attwood J.T., Bondarev I., Pashine A., Mellor A.L. Inhibition of T cell proliferation by macrophage tryptophan catabolism. The Journal of Experimental Medicine 1999, 189:1363-1372.
135. Nyugen J., Agrawal S., Gollapudi S., Gupta S. Impaired functions of peripheral blood monocyte subpopulations in aged humans. Journal of Clinical Immunology 2010, 30:806-813.
136. Ogata K., Yokose N., Tamura H., An E., Nakamura K., Dan K., Nomura T. Natural killer cells in the late decades of human life. Clinical Immunology and Immunopathology 1997, 84:269-275.
137. Pamplona R., Portero-Otin M., Riba D., Ruiz C., Prat J., Bellmunt M.J., Barja G. Mitochondrial membrane peroxidizability index is inversely related to maximum life span in mammals. Journal of Lipid Research 1998, 39:1989-1994.
138. Paradis M.R. Demographics of health and disease in the geriatric horse. The Veterinary clinics of North America. Equine Practice 2002, 18:391-401.
139. Peres A., Bauer M., da Cruz I.B., Nardi N.B., Chies J.A. Immunophenotyping and T-cell proliferative capacity in a healthy aged population. Biogerontology 2003, 4:289-296.
140. Pirie R.S., Collie D.D., Dixon P.M., McGorum B.C. Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma). Clinical & Experimental Allergy 2003, 33:676-683.
141. Ralston S.L. Clinical nutrition of adult horses. The Veterinary Clinics of North America. Equine Practice 1990, 6:339-354.
142. Ralston S.L., Nockels C.F., Squires E.L. Differences in diagnostic test results and hematologic data between aged and young horses. American Journal of Veterinary Research 1988, 49:1387-1392.
143. Robbin M.G., Wagner B., Noronha L.E., Antczak D.F., de Mestre A.M. Subpopulations of equine blood lymphocytes expressing regulatory T cell markers. Veterinary Immunology and Immunopathology 2011, 140:90-101.
144. Ryan A.S., Nicklas B.J. Reductions in plasma cytokine levels with weight loss improve insulin sensitivity in overweight and obese postmenopausal women. Diabetes Care 2004, 27:1699-1705.
145. Sakaguchi S., Miyara M., Costantino C.M., Hafler D.A. FOXP3+ regulatory T cells in the human immune system. Nature reviews. Immunology 2010, 10:490-500.
146. Sarli G., Peli A., Marrocco R., Zanotti L., Ducci A., Isani G., Alessandra S., Sassi F., Benazzi C., Cinotti S., Pietra M. A comparison of IL-1 beta and IL-8 mRNA and their respective proteins in equine bronchoalveolar lavage fluid during recurrent airway obstruction. Online Journal of Veterinary Research 2011, 2011.
147. Saurwein-Teissl M., Blasko I., Zisterer K., Neuman B., Lang B., Grubeck-Loebenstein B. An imbalance between pro- and anti-inflammatory cytokines, a characteristic feature of old age. Cytokine 2000, 12:1160-1161.
148. Saurwein-Teissl M., Lung T.L., Marx F., Gschosser C., Asch E., Blasko I., Parson W., Bock G., Schonitzer D., Trannoy E., Grubeck-Loebenstein B. Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. Journal of Immunology 2002, 168:5893-5899.
149. Savale L., Chaouat A., Bastuji-Garin S., Marcos E., Boyer L., Maitre B., Sarni M., Housset B., Weitzenblum E., Matrat M., Le Corvoisier P., Rideau D., Boczkowski J., Dubois-Rande J.L., Chouaid C., Adnot S. Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2009, 179:566-571.
150. Schroder K., Hertzog P.J., Ravasi T., Hume D.A. Interferon-gamma: an overview of signals, mechanisms and functions. Journal of Leukocyte biology 2004, 75:163-189.
151. Stout R.D., Suttles J. Functional plasticity of macrophages: reversible adaptation to changing microenvironments. Journal of Leukocyte Biology 2004, 76:509-513.
152. Suagee J.K., Corl B.A., Crisman M.V., Pleasant R.S., Thatcher C.D., Geor R.J. Relationships between body condition score and plasma inflammatory cytokines, insulin, and lipids in a mixed population of light-breed horses. Journal of Veterinary Internal Medicine/American College of Veterinary Internal Medicine 2013, 27:157-163.
153. Suganami T., Nishida J., Ogawa Y. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arteriosclerosis, Thrombosis, and Vascular Biology 2005, 25:2062-2068.
154. Sun L., Adams A.A., Betancourt A., Stewart J.C., Liu C., Horohov D.W. The role of proliferation in the regulation of interferon gamma (IFNgamma) expression in foals. Developmental and Comparative Immunology 2012, 36:534-539.
155. Sun L., Adams A.A., Page A.E., Betancourt A., Horohov D.W. The effect of environment on interferon-gamma production in neonatal foals. Veterinary Immunology and Immunopathology 2011, 143:170-175.
156. Svartengren M., Falk R., Philipson K. Long-term clearance from small airways decreases with age. The European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology 2005, 26:609-615.
157. Swain S., Clise-Dwyer K., Haynes L. Homeostasis and the age-associated defect of CD4T cells. Seminars in Immunology 2005, 17:370-377.
158. Takabayshi K., Corr M., Hayashi T., Redecke V., Beck L., Guiney D., Sheppard D., Raz E. Induction of a homeostatic circuit in lung tissue by microbial compounds. Immunity 2006, 24:475-487.
159. Takabayshi K., Corr M., Hayashi T., Redecke V., Beck L., Guiney D., Sheppard D., Raz E. Retraction. Induction of a homeostatic circuit in lung tissue by microbial compounds. Immunity 2008, 28:724.
160. Tasat D.R., Mancuso R., O'Connor S., Molinari B. Age-dependent change in reactive oxygen species and nitric oxide generation by rat alveolar macrophages. Aging Cell 2003, 2:159-164.
161. Taylor M.W., Feng G.S. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 1991, 5:2516-2522.
162. Theegarten D., Mogilevski G., Anhenn O., Stamatis G., Jaeschock R., Morgenroth K. The role of chlamydia in the pathogenesis of pulmonary emphysema. Electron microscopy and immunofluorescence reveal corresponding findings as in atherosclerosis. Virchows Archive: An International Journal of Pathology 2000, 437:190-193.
163. Theegarten D., Sachse K., Mentrup B., Fey K., Hotzel H., Anhenn O. Chlamydophila spp. infection in horses with recurrent airway obstruction: similarities to human chronic obstructive disease. Respiratory Research 2008, 9:14.
164. Thepen T., Van Rooijen N., Kraal G. Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. The Journal of Experimental Medicine 1989, 170:499-509.
165. Thompson A.B., Scholer S.G., Daughton D.M., Potter J.F., Rennard S.I. Altered epithelial lining fluid parameters in old normal individuals. Journal of Gerontology 1992, 47:M171-M176.
166. Tsuji T., Aoshiba K., Nagai A. Alveolar cell senescence exacerbates pulmonary inflammation in patients with chronic obstructive pulmonary disease. Respiration: International Review of Thoracic Diseases 2010, 80:59-70.
167. Turner J.M., Mead J., Wohl M.E. Elasticity of human lungs in relation to age. Journal of Applied Physiology 1968, 25:664-671.
168. Ueda T., Cheng G., Kuroki Y., Sano H., Sugiyama K., Motojima S., Fukuda T. Effects of aging on surfactant forms in rats. The European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology 2000, 15:80-84.
169. UN (United Nations) Report, Department of Economic and Social Affairs Population Division: World population ageing 1950-2050 2002, Report prepared for the 2nd World Assembly on Ageing (2002) United Nations Publishing, New York, NY.
170. van Duin D., Mohanty S., Thomas V., Ginter S., Montgomery R.R., Fikrig E., Allore H.G., Medzhitov R., Shaw A.C. Age-associated defect in human TLR-1/2 function. Journal of Immunology 2007, 178:970-975.
171. Verbeken E.K., Cauberghs M., Mertens I., Clement J., Lauweryns J.M., Van de Woestijne K.P. The senile lung. Comparison with normal and emphysematous lungs. 1. Structural aspects. Chest 1992, 101:793-799.
172. Verbeken E.K., Cauberghs M., Mertens I., Clement J., Lauweryns J.M., Van de Woestijne K.P. The senile lung. Comparison with normal and emphysematous lungs. 2. Functional aspects. Chest 1992, 101:800-809.
173. Villanueva J.L., Solana R., Alonso M.C., Pena J. Changes in the expression of HLA-class II antigens on peripheral blood monocytes from aged humans. Disease Markers 1990, 8:85-91.
174. Walford R.L. The Immunologic Theory of Aging. The Gerontologist 1964, 57:195-197.
175. Walski M., Pokorski M., Antosiewicz J., Rekawek A., Frontczak-Baniewicz M., Jernajczyk U., Di Giulio C. Pulmonary surfactant: ultrastructural features and putative mechanisms of aging. Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society 2009, 60(Suppl 5):121-125.
176. Wang J.Y., Reid K.B. The immunoregulatory roles of lung surfactant collectins SP-A, and SP-D, in allergen-induced airway inflammation. Immunobiology 2007, 212:417-425.
177. Wenisch C., Patruta S., Daxbock F., Krause R., Horl W. Effect of age on human neutrophil function. Journal of Leukocyte Biology 2000, 67:40-45.
178. Wert S.E., Yoshida M., LeVine A.M., Ikegami M., Jones T., Ross G.F., Fisher J.H., Korfhagen T.R., Whitsett J.A. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proceedings of the National Academy of Sciences of the United States of America 2000, 97:5972-5977.
179. Wewers M.D., Rennard S.I., Hance A.J., Bitterman P.B., Crystal R.G. Normal human alveolar macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin-1. The Journal of Clinical Investigation 1984, 74:2208-2218.
180. Wiese A.G., Pacifici R.E., Davies K.J. Transient adaptation of oxidative stress in mammalian cells. Archives of Biochemistry and Biophysics 1995, 318:231-240.
181. Wiester M.J., Tepper J.S., Winsett D.W., Crissman K.M., Richards J.H., Costa D.L. Adaptation to ozone in rats and its association with ascorbic acid in the lung. Fundamental and Applied Toxicology: Official Journal of the Society of Toxicology 1996, 31:56-64.
182. Williams C.A., Gordon M.E., Betros C.L., McKeever K.H. Apoptosis and antioxidant status are influenced by age and exercise training in horses. Journal of Animal Science 2008, 86:576-583.
183. Wu D., Meydani S.N. Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention. Journal of Leukocyte Biology 2008, 84:900-914.
184. Yang S.R., Chida A.S., Bauter M.R., Shafiq N., Seweryniak K., Maggirwar S.B., Kilty I., Rahman I. Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages. American Journal of Physiology, Lung Cellular and Molecular Physiology 2006, 291:L46-L57.
185. Yang X., Stedra J., Cerny J. Relative contribution of T and B cells to hypermutation and selection of the antibody repertoire in germinal centers of aged mice. The Journal of Experimental Medicine 1996, 183:959-970.
186. Zeng G., McCue H.M., Mastrangelo L., Millis A.J. Endogenous TGF-beta activity is modified during cellular aging: effects on metalloproteinase and TIMP-1 expression. Experimental Cell Research 1996, 228:271-276.
187. Zheng B., Han S., Takahashi Y., Kelsoe G. Immunosenescence and germinal center reaction. Immunological Reviews 1997, 160:63-77.
188. Zhou T., Edwards C.K., Mountz J.D. Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice. The Journal of Experimental Medicine 1995, 182:129-137.
189. Zinyama R.B., Bancroft G.J., Sigola L.B. Adrenaline suppression of the macrophage nitric oxide response to lipopolysaccharide is associated with differential regulation of tumour necrosis factor-alpha and interleukin-10. Immunology 2001, 104:439-446.
190. Zissel G., Schlaak M., Muller-Quernheim J. Age-related decrease in accessory cell function of human alveolar macrophages. Journal of Investigative Medicine: The Official Publication of the American Federation for Clinical Research 1999, 47:51-56.