The effects of antigen-specific IgG1 antibody for the pulmonary-hypertension-phenotype and B cells for inflammation in mice exposed to antigen and fine particles from air pollution

PLoS ONE

Volumn 10, Issue 6, 2015, Pages

  Park, Sung Hyun ^a   Chen, Wen Chi ^a   Durmus, Nedim ^a   Bleck, Bertram ^a   Reibman, Joan ^a   Riemekasten, Gabriela ^b   Grunig, Gabriele ^a  

^a NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF LÜBECK   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN G1 ANTIBODY; INTERLEUKIN 13; INTERLEUKIN 17; AIR POLLUTANT; ANTIGEN; IMMUNOGLOBULIN G; PARTICULATE MATTER;

AIR POLLUTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY RESPONSE; ANTIGEN SPECIFICITY; ARTICLE; B LYMPHOCYTE; CONTROLLED STUDY; HEART RIGHT VENTRICLE HYPERTROPHY; HEART RIGHT VENTRICLE PRESSURE; INFLAMMATION; MOUSE; NONHUMAN; PARTICULATE MATTER; PHENOTYPE; PULMONARY HYPERTENSION; SYSTOLIC BLOOD PRESSURE; VASCULAR REMODELING; WILD TYPE; ADVERSE EFFECTS; AIR POLLUTANT; ANIMAL; ANTIBODY SPECIFICITY; BLOOD PRESSURE; DRUG EFFECTS; IMMUNOLOGY; PATHOLOGY; PATHOPHYSIOLOGY; PULMONARY ARTERY;

MUS;

AIR POLLUTANTS; ANIMALS; ANTIBODY SPECIFICITY; ANTIGENS; B-LYMPHOCYTES; BLOOD PRESSURE; HYPERTENSION, PULMONARY; IMMUNOGLOBULIN G; MICE; PARTICULATE MATTER; PHENOTYPE; PULMONARY ARTERY;

EID: 84937957463     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0129910     Document Type: Article

References (81)

1. Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest. 2012; 122 (12):4306-13. doi: 10.1172/JCI60658 PMID: 23202738; PubMed Central PMCID: PMC3533531.
2. Barst RJ, Gibbs JS, Ghofrani HA, Hoeper MM, McLaughlin VV, Rubin LJ, et al. Updated evidencebased treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009; 54(1 Suppl): S78-84. doi: 10.1016/j.jacc.2009.04.017 PMID: 19555861.
3. Fritz JS, Blair C, Oudiz RJ, Dufton C, Olschewski H, Despain D, et al. Baseline and follow-up 6-min walk distance and brain natriuretic peptide predict 2-year mortality in pulmonary arterial hypertension. Chest. 2013; 143(2):315-23. doi: 10.1378/chest.12-0270 PMID: 22814814.
4. Bogaard HJ, Natarajan R, Henderson SC, Long CS, Kraskauskas D, Smithson L, et al. Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation. 2009; 120 (20):1951-60. doi: 10.1161/CIRCULATIONAHA.109.883843 PMID: 19884466.
5. Grunig G, Marsh LM, Esmaeil N, Jackson K, Gordon T, Reibman J, et al. Perspective: ambient air pollution: inflammatory response and effects on the lung's vasculature. Pulmonary circulation. 2014; 4:25-35. doi: 10.1086/674902 PMID: 25006418
6. Esmaeil N, Gharagozloo M, Rezaei A, Grunig G. Dust events, pulmonary diseases and immune system. American journal of clinical and experimental immunology. 2014; 3(1):20-9. PMID: 24660118; PubMed Central PMCID: PMC3960758.
7. Scano G, Garcia-Herreros P, Stendardi D, Degre S, De Coster A, Sergysels R. Cardiopulmonary adaptation to exercise in coal miners. Archives of environmental health. 1980; 35(6):360-6. PMID: 7458418.
8. Makellar A. An Investigation into the Nature of Black Phthisis; or Ulceration Induced by Carbonaceous Accumulation in Lungs of Coal Miners and Other Operatives. Medico-Chirurgical Society of Edinburgh; from the Scottish Mining Website. 1846.
9. World-Health-Organization. Silicosis. Geneva: World Health Organization; 2000. 4 p. p.
10. Seimetz M, Parajuli N, Pichl A, Veit F, Kwapiszewska G, Weisel FC, et al. Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice. Cell. 2011; 147 (2):293-305. Epub 2011/10/18. doi: 10.1016/j.cell.2011.08.035 PMID: 22000010.
11. Leary PJ, Kaufman JD, Barr RG, Bluemke DA, Curl CL, Hough CL, et al. Traffic-related air pollution and the right ventricle. The multi-ethnic study of atherosclerosis. Am J Respir Crit Care Med. 2014; 189 (9):1093-100. doi: 10.1164/rccm.201312-2298OC PMID: 24593877; PubMed Central PMCID: PMC4098110.
12. Miller FW, Alfredsson L, Costenbader KH, Kamen DL, Nelson LM, Norris JM, et al. Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop. Journal of autoimmunity. 2012; 39(4):259-71. doi: 10. 1016/j.jaut.2012.05.002 PMID: 22739348; PubMed Central PMCID: PMC3496812.
13. Parks CG, Miller FW, Pollard KM, Selmi C, Germolec D, Joyce K, et al. Expert panel workshop consensus statement on the role of the environment in the development of autoimmune disease. International journal of molecular sciences. 2014; 15(8):14269-97. doi: 10.3390/ijms150814269 PMID: 25196523; PubMed Central PMCID: PMC4159850.
14. Chaisson NF, Hassoun PM. Systemic sclerosis-associated pulmonary arterial hypertension. Chest. 2013; 144(4):1346-56. Epub 2013/10/02. doi: 10.1378/chest.12-2396 PMID: 24081346; PubMed Central PMCID: PMC3787920.
15. Daley E, Emson C, Guignabert C, de Waal Malefyt R, Louten J, Kurup VP, et al. Pulmonary arterial remodeling induced by a Th2 immune response. The Journal of experimental medicine. 2008; 205 (2):361-72. doi: 10.1084/jem.20071008 PMID: 18227220; PubMed Central PMCID: PMC2271018.
16. Park SH, Chen WC, Esmaeil N, Lucas BEG, Marsh LM, Reibman J, et al. IL-13 and IL-17A induced pulmonary- hypertension-phenotype due to inhalation of antigen and fine particles from air pollution. Pulmonary circulation. 2014; 4(4):654-68. doi: 10.1086/678511 PMID: 25610601
17. Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, et al. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol. 2009; 54(1 Suppl):S10-9. doi: 10. 1016/j.jacc.2009.04.006 PMID: 19555853.
18. Tuder RM, Archer SL, Dorfmuller P, Erzurum SC, Guignabert C, Michelakis E, et al. Relevant issues in the pathology and pathobiology of pulmonary hypertension. J Am Coll Cardiol. 2013; 62(25 Suppl):D4-12, doi: 10.1016/j.jacc.2013.10.025 PMID: 24355640; PubMed Central PMCID: PMC3970402.
19. Rabinovitch M, Guignabert C, Humbert M, Nicolls MR. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension. Circ Res. 2014; 115(1):165-75. doi: 10.1161/CIRCRESAHA.113. 301141 PMID: 24951765; PubMed Central PMCID: PMC4097142.
20. Colvin KL, Cripe PJ, Ivy DD, Stenmark KR, Yeager ME. Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies. Am J Respir Crit Care Med. 2013; 188 (9):1126-36. doi: 10.1164/rccm.201302-0403OC PMID: 24093638; PubMed Central PMCID: PMC3863738.
21. Morse JH, Antohi S, Kasturi K, Saito S, Fotino M, Humbert M, et al. Fine specificity of anti-fibrillin-1 autoantibodies in primary pulmonary hypertension syndrome. Scandinavian journal of immunology. 2000; 51(6):607-11. PMID: 10849372.
22. Dib H, Tamby MC, Bussone G, Regent A, Berezne A, Lafine C, et al. Targets of anti-endothelial cell antibodies in pulmonary hypertension and scleroderma. Eur Respir J. 2012; 39(6):1405-14. doi: 10.1183/ 09031936.00181410 PMID: 22005913.
23. Ulrich S, Taraseviciene-Stewart L, Huber LC, Speich R, Voelkel N. Peripheral blood B lymphocytes derived from patients with idiopathic pulmonary arterial hypertension express a different RNA pattern compared with healthy controls: a cross sectional study. Respir Res. 2008; 9:20. doi: 10.1186/1465- 9921-9-20 PMID: 18269757; PubMed Central PMCID: PMC2262076.
24. Becker MO, Kill A, Kutsche M, Guenther J, Rose A, Tabeling C, et al. Vascular receptor autoantibodies in pulmonary arterial hypertension associated with systemic sclerosis. Am J Respir Crit Care Med. 2014; 190(7):808-17. doi: 10.1164/rccm.201403-0442OC PMID: 25181620.
25. Arends SJ, Damoiseaux J, Duijvestijn A, Debrus-Palmans L, Boomars K, Broers B, et al. Prevalence of anti-endothelial cell antibodies in idiopathic pulmonary arterial hypertension. Eur Respir J. 2010; 35 (4):923-5. doi: 10.1183/09031936.00164209 PMID: 20356989.
26. Arends SJ, Damoiseaux JG, Duijvestijn AM, Debrus-Palmans L, Boomars KA, Brunner-La Rocca HP, et al. Functional implications of IgG anti-endothelial cell antibodies in pulmonary arterial hypertension. Autoimmunity. 2013; 46(7):463-70. doi: 10.3109/08916934.2013.812080 PMID: 24083390.
27. Arends SJ, Damoiseaux JG, Duijvestijn AM, Debrus-Palmans L, Vroomen M, Boomars KA, et al. Immunoglobulin G anti-endothelial cell antibodies: inducers of endothelial cell apoptosis in pulmonary arterial hypertension? Clinical and experimental immunology. 2013; 174(3):433-40. doi: 10.1111/cei.12166 PMID: 23815467; PubMed Central PMCID: PMC3826309.
28. Bussone G, Dib H, Tamby MC, Broussard C, Federici C, Woimant G, et al. Identification of new autoantibody specificities directed at proteins involved in the transforming growth factor beta pathway in patients with systemic sclerosis. Arthritis Res Ther. 2011; 13(3):R74. doi: 10.1186/ar3336 PMID: 21569507; PubMed Central PMCID: PMC3218884.
29. Bussone G, Tamby MC, Calzas C, Kherbeck N, Sahbatou Y, Sanson C, et al. IgG from patients with pulmonary arterial hypertension and/or systemic sclerosis binds to vascular smooth muscle cells and induces cell contraction. Annals of the rheumatic diseases. 2012; 71(4):596-605. doi: 10.1136/ annrheumdis-2011-200195 PMID: 22084393.
30. Kill A, Tabeling C, Undeutsch R, Kuhl AA, Gunther J, Radic M, et al. Autoantibodies to angiotensin and endothelin receptors in systemic sclerosis induce cellular and systemic events associated with disease pathogenesis. Arthritis Res Ther. 2014; 16(1):R29. doi: 10.1186/ar4457 PMID: 24472528; PubMed Central PMCID: PMC3978438.
31. Riemekasten G, Philippe A, Nather M, Slowinski T, Muller DN, Heidecke H, et al. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Annals of the rheumatic diseases. 2011; 70(3):530-6. doi: 10.1136/ard.2010.135772 PMID: 21081526.
32. Nimmerjahn F, Ravetch JV. The antiinflammatory activity of IgG: the intravenous IgG paradox. J Exp Med. 2007; 204(1):11-5. doi: 10.1084/jem.20061788 PMID: 17227911; PubMed Central PMCID: PMC2118416.
33. Baumann U, Chouchakova N, Gewecke B, Kohl J, Carroll MC, Schmidt RE, et al. Distinct tissue sitespecific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex- induced injury of skin and lung. J Immunol. 2001; 167(2):1022-7. PMID: 11441111.
34. Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014; 9:181-218. doi: 10.1146/annurev-pathol-020712-164023 PMID: 24050624.
35. Guilliams M, Bruhns P, Saeys Y, Hammad H, Lambrecht BN. The function of Fcgamma receptors in dendritic cells and macrophages. Nat Rev Immunol. 2014; 14(2):94-108. doi: 10.1038/nri3582 PMID: 24445665.
36. Li F, Smith P, Ravetch JV. Inhibitory Fcgamma receptor is required for the maintenance of tolerance through distinct mechanisms. J Immunol. 2014; 192(7):3021-8. doi: 10.4049/jimmunol.1302934 PMID: 24563255; PubMed Central PMCID: PMC3967505.
37. Karsten CM, Pandey MK, Figge J, Kilchenstein R, Taylor PR, Rosas M, et al. Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcgammaRIIB and dectin-1. Nat Med. 2012; 18(9):1401-6. doi: 10.1038/nm.2862 PMID: 22922409; PubMed Central PMCID: PMC3492054.
38. Desai DD, Harbers SO, Flores M, Colonna L, Downie MP, Bergtold A, et al. Fc gamma receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses. J Immunol. 2007; 178(10):6217-26. PMID: 17475849.
39. Ishikawa Y, Kobayashi K, Yamamoto M, Nakata K, Takagawa T, Funada Y, et al. Antigen-Specific IgG ameliorates allergic airway inflammation via Fcgamma receptor IIB on dendritic cells. Respir Res. 2011; 12:42. doi: 10.1186/1465-9921-12-42 PMID: 21477339; PubMed Central PMCID: PMC3079623.
40. Gilmour MI, McGee J, Duvall RM, Dailey L, Daniels M, Boykin E, et al. Comparative toxicity of size-fractionated airborne particulate matter obtained from different cities in the United States. Inhal Toxicol. 2007; 19 Suppl 1:7-16. doi: 10.1080/08958370701490379 PMID: 17886044.
41. Park SH, Chen WC, Hoffman C, Marsh LM, West J, Grunig G. Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene. PLoS One. 2013; 8(1):e55180. doi: 10.1371/journal.pone.0055180 PMID: 23383100; PubMed Central PMCID: PMC3558423.
42. Chen WC, Park SH, Hoffman C, Philip C, Robinson L, West J, et al. Right ventricular systolic pressure measurements in combination with harvest of lung and immune tissue samples in mice. Journal of visualized experiments: JoVE. 2013;(71: ):e50023. doi: 10.3791/50023 PMID: 23354416; PubMed Central PMCID: PMC3582655.
43. Hoffman C, Park SH, Daley E, Emson C, Louten J, Sisco M, et al. Interleukin-19: a constituent of the regulome that controls antigen presenting cells in the lungs and airway responses to microbial products. PLoS One. 2011; 6(11):e27629. doi: 10.1371/journal.pone.0027629 PMID: 22110701; PubMed Central PMCID: PMC3217014.
44. Padilla J, Daley E, Chow A, Robinson K, Parthasarathi K, McKenzie AN, et al. IL-13 Regulates the Immune Response to Inhaled Antigens. J Immunol. 2005; 174(12):8097-105. PMID: 15944318.
45. Grunig G, Corry DB, Leach MW, Seymour BW, Kurup VP, Rennick DM. Interleukin-10 is a natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis. J Exp Med. 1997; 185(6):1089-99. PMID: 9091582
46. Ford JG, Rennick D, Donaldson DD, Venkayya R, McArthur C, Hansell E, et al. IL-13 and IFN-gamma: interactions in lung inflammation. J Immunol. 2001; 167(3):1769-77. PMID: 11466402.
47. Kuroda E, Ishii KJ, Uematsu S, Ohata K, Coban C, Akira S, et al. Silica crystals and aluminum salts regulate the production of prostaglandin in macrophages via NALP3 inflammasome-independent mechanisms. Immunity. 2011; 34(4):514-26. doi: 10.1016/j.immuni.2011.03.019 PMID: 21497116.
48. Polikepahad S, Knight JM, Naghavi AO, Oplt T, Creighton CJ, Shaw C, et al. Proinflammatory role for let-7 microRNAS in experimental asthma. J Biol Chem. 2010; 285(39):30139-49. Epub 2010/07/16. doi: 10.1074/jbc.M110.145698 PMID: 20630862; PubMed Central PMCID: PMC2943272.
49. Foell D, Wittkowski H, Vogl T, Roth J. S100 proteins expressed in phagocytes: a novel group of damage- associated molecular pattern molecules. Journal of leukocyte biology. 2007; 81(1):28-37. Epub 2006/09/01. doi: 10.1189/jlb.0306170 PMID: 16943388.
50. Jin S, Park CO, Shin JU, Noh JY, Lee YS, Lee NR, et al. DAMP molecules S100A9 and S100A8 activated by IL-17A and house-dust mites, are increased in atopic dermatitis. Experimental dermatology. 2014. doi: 10.1111/exd.12563 PMID: 25308296.
51. Humbert M, Monti G, Brenot F, Sitbon O, Portier A, Grangeot-Keros L, et al. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med. 1995; 151(5):1628-31. PMID: 7735624.
52. Mayadas TN, Tsokos GC, Tsuboi N. Mechanisms of immune complex-mediated neutrophil recruitment and tissue injury. Circulation. 2009; 120(20):2012-24. doi: 10.1161/CIRCULATIONAHA.108.771170 PMID: 19917895; PubMed Central PMCID: PMC2782878.
53. Johnson JA, West J, Maynard KB, Hemnes AR. ACE2 improves right ventricular function in a pressure overload model. PLoS One. 2011; 6(6):e20828. doi: 10.1371/journal.pone.0020828 PMID: 21695173; PubMed Central PMCID: PMC3112229.
54. Liew FY, Pitman NI, McInnes IB. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol. 2010; 10(2):103-10. doi: 10.1038/nri2692 PMID: 20081870.
55. Mishra A, Wang M, Schlotman J, Nikolaidis NM, DeBrosse CW, Karow ML, et al. Resistin-like molecule- beta is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung. Am J Physiol Lung Cell Mol Physiol. 2007; 293(2):L305-13. Epub 2007/06/05. doi: 10.1152/ajplung. 00147.2007 PMID: 17545488.
56. Nair MG, Du Y, Perrigoue JG, Zaph C, Taylor JJ, Goldschmidt M, et al. Alternatively activated macrophage- derived RELM-{alpha} is a negative regulator of type 2 inflammation in the lung. J Exp Med. 2009; 206(4):937-52. PMID: 19349464. doi: 10.1084/jem.20082048
57. Pesce JT, Ramalingam TR, Wilson MS, Mentink-Kane MM, Thompson RW, Cheever AW, et al. Retnla (relmalpha/fizz1) suppresses helminth-induced th2-type immunity. PLoS Pathog. 2009; 5(4): e1000393. PMID: 19381262. doi: 10.1371/journal.ppat.1000393
58. Yamaji-Kegan K, Takimoto E, Zhang A, Weiner NC, Meuchel LW, Berger AE, et al. Hypoxia-induced mitogenic factor (FIZZ1/RELMalpha) induces endothelial cell apoptosis and subsequent interleukin-4- dependent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2014; 306(12):L1090-103. doi: 10.1152/ajplung.00279.2013 PMID: 24793164; PubMed Central PMCID: PMC4060011.
59. Teng X, Li D, Champion HC, Johns RA. FIZZ1/RELMalpha, a novel hypoxia-induced mitogenic factor in lung with vasoconstrictive and angiogenic properties. Circ Res. 2003; 92(10):1065-7. PMID: 12714564.
60. Renigunta A, Hild C, Rose F, Klepetko W, Grimminger F, Seeger W, et al. Human RELMbeta is a mitogenic factor in lung cells and induced in hypoxia. FEBS Lett. 2006; 580(3):900-3. PMID: 16427636.
61. Munitz A, Seidu L, Cole ET, Ahrens R, Hogan SP, Rothenberg ME. Resistin-like molecule alpha decreases glucose tolerance during intestinal inflammation. J Immunol. 2009; 182(4):2357-63. doi: 10. 4049/jimmunol.0803130 PMID: 19201890; PubMed Central PMCID: PMC2653277.
62. Gerstmayer B, Kusters D, Gebel S, Muller T, Van Miert E, Hofmann K, et al. Identification of RELMgamma, a novel resistin-like molecule with a distinct expression pattern. Genomics. 2003; 81 (6):588-95. PMID: 12782128.
63. Shojima N, Ogihara T, Inukai K, Fujishiro M, Sakoda H, Kushiyama A, et al. Serum concentrations of resistin-like molecules beta and gamma are elevated in high-fat-fed and obese db/db mice, with increased production in the intestinal tract and bone marrow. Diabetologia. 2005; 48(5):984-92. doi: 10. 1007/s00125-005-1735-1 PMID: 15834545.
64. Oshiba A, Hamelmann E, Takeda K, Bradley KL, Loader JE, Larsen GL, et al. Passive transfer of immediate hypersensitivity and airway hyperresponsiveness by allergen-specific immunoglobulin (Ig) E and IgG1 in mice. J Clin Invest. 1996; 97(6):1398-408. doi: 10.1172/JCI118560 PMID: 8617871; PubMed Central PMCID: PMC507198.
65. Medesan C, Matesoi D, Radu C, Ghetie V, Ward ES. Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgG1. J Immunol. 1997; 158(5):2211-7. PMID: 9036967.
66. Faquim-Mauro EL, Coffman RL, Abrahamsohn IA, Macedo MS. Cutting edge: mouse IgG1 antibodies comprise two functionally distinct types that are differentially regulated by IL-4 and IL-12. J Immunol. 1999; 163(7):3572-6. PMID: 10490948.
67. Lefrancais E, Duval A, Mirey E, Roga S, Espinosa E, Cayrol C, et al. Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells. Proc Natl Acad Sci U S A. 2014; 111(43):15502-7. doi: 10.1073/pnas.1410700111 PMID: 25313073; PubMed Central PMCID: PMC4217470.
68. Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, et al. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS pathogens. 2008; 4(9):e1000159. doi: 10.1371/journal.ppat. 1000159 PMID: 18802458; PubMed Central PMCID: PMC2528945.
69. Wright JL, Tai H, Wang R, Wang X, Churg A. Cigarette smoke upregulates pulmonary vascular matrix metalloproteinases via TNF-alpha signaling. Am J Physiol Lung Cell Mol Physiol. 2007; 292(1):L125-33, doi: 10.1152/ajplung.00539.2005 PMID: 16905636.
70. Chelladurai P, Seeger W, Pullamsetti SS. Matrix metalloproteinases and their inhibitors in pulmonary hypertension. Eur Respir J. 2012; 40(3):766-82. doi: 10.1183/09031936.00209911 PMID: 22523364.
71. Biasin V, Marsh LM, Egemnazarov B, Wilhelm J, Ghanim B, Klepetko W, et al. Meprin beta, a novel mediator of vascular remodelling underlying pulmonary hypertension. J Pathol. 2014; 233(1):7-17. doi: 10.1002/path.4303 PMID: 24258247.
72. Zaidi SH, You XM, Ciura S, Husain M, Rabinovitch M. Overexpression of the serine elastase inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension. Circulation. 2002; 105(4):516-21, PMID: 11815437.
73. Kim YM, Haghighat L, Spiekerkoetter E, Sawada H, Alvira CM, Wang L, et al. Neutrophil elastase is produced by pulmonary artery smooth muscle cells and is linked to neointimal lesions. Am J Pathol. 2011; 179(3):1560-72. doi: 10.1016/j.ajpath.2011.05.051 PMID: 21763677; PubMed Central PMCID: PMC3157285.
74. Angelini DJ, Su Q, Yamaji-Kegan K, Fan C, Skinner JT, Poloczek A, et al. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMalpha) in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling. Respir Res. 2013; 14:1. doi: 10.1186/1465-9921-14-1 PMID: 23289668; PubMed Central PMCID: PMC3547770.
75. Bloomfield GS, Lagat DK, Akwanalo OC, Carter EJ, Lugogo N, Vedanthan R, et al. Waiting to inhale: An exploratory review of conditions that may predispose to pulmonary hypertension and right heart failure in persons exposed to household air pollution in low- and middle-income countries. Global heart. 2012; 7(3):249-59. doi: 10.1016/j.gheart.2012.06.015 PMID: 23687634; PubMed Central PMCID: PMC3653331.
76. Holguin F, McCormack MC. Right from wrong: the effect of traffic-related pollution on the right heart. Am J Respir Crit Care Med. 2014; 189(9):1018-9. doi: 10.1164/rccm.201404-0613ED PMID: 24787063.
77. Su Q, Zhou Y, Johns RA. Bruton's tyrosine kinase (BTK) is a binding partner for hypoxia induced mitogenic factor (HIMF/FIZZ1) and mediates myeloid cell chemotaxis. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2007. PMID: 17264170.
78. Park K, Park JH, Yang WJ, Lee JJ, Song MJ, Kim HP. Transcriptional activation of the IL31 gene by NFAT and STAT6. J Leukoc Biol. 2012; 91(2):245-57. doi: 10.1189/jlb.0111020 PMID: 22045870.
79. Said SI, Hamidi SA, Gonzalez Bosc L. Asthma and pulmonary arterial hypertension: do they share a key mechanism of pathogenesis? Eur Respir J. 2010; 35(4):730-4. Epub 2010/04/02. doi: 35/4/730 [pii]doi: 10.1183/09031936.00097109 PMID: 20356986; PubMed Central PMCID: PMC2963099.
80. Michelakis ED, Wilkins MR, Rabinovitch M. Emerging concepts and translational priorities in pulmonary arterial hypertension. Circulation. 2008; 118(14):1486-95. doi: 10.1161/CIRCULATIONAHA.106. 673988 PMID: 18824655.
81. Sanchez O, Sitbon O, Jais X, Simonneau G, Humbert M. Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension. Chest. 2006; 130(1):182-9. PMID: 16840400.