Targeting granulocyte apoptosis: Mechanisms, models, and therapies

Immunological Reviews

Volumn 236, Issue 1, 2010, Pages 28-40

  Duffin, Rodger ^a   Leitch, Andrew E ^a   Fox, Sarah ^a   Haslett, Chris ^a   Rossi, Adriano G ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Apoptosis; Basophil; Eosinophil; Inflammation; Neutrophil; Phagocytosis

Indexed keywords

GLUCOCORTICOID;

ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; AUTOPHAGY; BASOPHIL; CELL DIFFERENTIATION; CELL FUNCTION; CELL LINEAGE; CELL MATURATION; CELL STRUCTURE; CELL SURVIVAL; EOSINOPHIL; GRANULOCYTE; HUMAN; INFLAMMATION; LIFE CYCLE; MACROPHAGE; MONOCYTE; MULTIPOTENT STEM CELL; NEUTROPHIL; NONHUMAN; PHAGOCYTOSIS; PRIORITY JOURNAL; REVIEW;

ANIMALS; APOPTOSIS; CELL DIFFERENTIATION; GRANULOCYTES; HUMANS; IMMUNE SYSTEM; INFLAMMATION; MACROPHAGES; MODELS, IMMUNOLOGICAL; PHAGOCYTOSIS;

EID: 77953764623     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2010.00922.x     Document Type: Review

References (134)

1. Serhan CN, et al. Resolution of inflammation: state of the art, definitions and terms. FASEB J 2007 21 : 325 332.
2. Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, Haslett C. Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J Clin Invest 1989 83 : 865 875.
3. Leitch AE, Duffin R, Haslett C, Rossi AG. Relevance of granulocyte apoptosis to resolution of inflammation at the respiratory mucosa. Mucosal Immunol 2008 1 : 350 363.
4. Haslett C. Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am J Respir Crit Care Med 1999 160 : S5 S11.
5. Hallett JM, Leitch AE, Riley NA, Duffin R, Haslett C, Rossi AG. Novel pharmacological strategies for driving inflammatory cell apoptosis and enhancing the resolution of inflammation. Trends Pharmacol Sci 2008 29 : 250 257.
6. Edwards SW. Biochemistry and Physiology of the Neutrophil.
7. Opferman JT. Life and death during hematopoietic differentiation. Curr Opin Immunol 2007 19 : 497 502.
8. Giembycz MA, Lindsay MA. Pharmacology of the eosinophil. Pharmacol Rev 1999 51 : 213 340.
9. Gauvreau GM, Ellis AK, Denburg JA. Haemopoietic processes in allergic disease: eosinophil/basophil development. Clin Exp Allergy 2009 39 : 1297 1306.
10. Skokowa J, et al. LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia. Nat Med 2006 12 : 1191 1197.
11. Skokowa J, Welte K. LEF-1 is a decisive transcription factor in neutrophil granulopoiesis. Ann NY Acad Sci 2007 1106 : 143 151.
12. Ueda Y, Cain DW, Kuraoka M, Kondo M, Kelsoe G. IL-1R type I-dependent hemopoietic stem cell proliferation is necessary for inflammatory granulopoiesis and reactive neutrophilia. J Immunol 2009 182 : 6477 6484.
13. Wang D, Paz-Priel I, Friedman AD. NF-kappa B p50 regulates C/EBP alpha expression and inflammatory cytokine-induced neutrophil production. J Immunol 2009 182 : 5757 5762.
14. Friedman AD. Transcriptional control of granulocyte and monocyte development. Oncogene 2007 26 : 6816 5928.
15. Leuenroth SJ, Grutkoski PS, Ayala A, Simms HH. The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes apoptosis. J Leukoc Biol 2000 68 : 158 166.
16. Sivertson KL, Seeds MC, Long DL, Peachman KK, Bass DA. The differential effect of dexamethasone on granulocyte apoptosis involves stabilization of Mcl-1L in neutrophils but not in eosinophils. Cell Immunol 2007 246 : 34 45.
17. Dick EP, Prince LR, Prestwich EC, Renshaw SA, Whyte MK, Sabroe I. Pathways regulating lipopolysaccharide-induced neutrophil survival revealed by lentiviral transduction of primary human neutrophils. Immunology 2009 127 : 249 255.
18. Rossi AG, Ward C, Dransfield I. Getting to grips with the granulocyte: manipulation of granulocyte behaviour and apoptosis by protein transduction methods. Biochem Soc Trans 2004 32 : 452 455.
19. Fujihara S, et al. Inhibition of nuclear factor-kappaB activation un-masks the ability of TNF-alpha to induce human eosinophil apoptosis. Eur J Immunol 2002 32 : 457 466.
20. Zemans RL, et al. A novel method for long term bone marrow culture and genetic modification of murine neutrophils via retroviral transduction. J Immunol Methods 2009 340 : 102 115.
21. Dick EP, Prince LR, Sabroe I. Ex vivo-expanded bone marrow CD34+ derived neutrophils have limited bactericidal ability. Stem Cells 2008 26 : 2552 2563.
22. Yokoyama Y, et al. Derivation of functional mature neutrophils from human embryonic stem cells. Blood 2009 113 : 6584 6592.
23. Rossi AG, et al. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med 2006 12 : 1056 1064.
24. Duffin R, et al. The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1. FEBS Lett 2009 583 : 2540 2546.
25. Leitch AE, et al. The cyclin-dependent kinase inhibitor R-roscovitine down-regulates Mcl-1 to override pro-inflammatory signalling and drive neutrophil apoptosis. Eur J Immunol 2010 40 : 1127 1138.
26. Leitch AE, Haslett C, Rossi AG. Cyclin-dependent kinase inhibitor drugs as potential novel anti-inflammatory and pro-resolution agents. Br J Pharmacol 2009 158 : 1004 1016.
27. Dhavan R, Tsai LH. A decade of CDK5. Nat Rev Mol Cell Biol 2001 2 : 749 759.
28. Klausen P, Bjerregaard MD, Borregaard N, Cowland JB. End-stage differentiation of neutrophil granulocytes in vivo is accompanied by up-regulation of p27kip1 and down-regulation of CDK2, CDK4, and CDK6. J Leukoc Biol 2004 75 : 569 578.
29. Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 2006 6 : 173 182.
30. Lambrecht BN, Hammad H. Biology of lung dendritic cells at the origin of asthma. Immunity 2009 31 : 412 424.
31. Eash KJ, Means JM, White DW, Link DC. CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions. Blood 2009 113 : 4711 4719.
32. Wengner AM, Pitchford SC, Furze RC, Rankin SM. The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation. Blood 2008 111 : 42 49.
33. Panopoulos AD, Watowich SS. Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis. Cytokine 2008 42 : 277 288.
34. Cara DC, Negrao-Correa D, Teixeira MM. Mechanisms underlying eosinophil trafficking and their relevance in vivo. Histol Histopathol 2000 15 : 899 920.
35. Baggiolini M. Chemokines and leukocyte traffic. Nature 1998 392 : 565 568.
36. Baggiolini M, Loetscher P. Chemokines in inflammation and immunity. Immunol Today 2000 21 : 418 420.
37. Petri B, Phillipson M, Kubes P. The physiology of leukocyte recruitment: an in vivo perspective. J Immunol 2008 180 : 6439 6446.
38. Sallusto F, Baggiolini M. Chemokines and leukocyte traffic. Nat Immunol 2008 9 : 949 952.
39. Sousa LP, et al. Cyclic AMP enhances resolution of allergic pleurisy by promoting inflammatory cell apoptosis via inhibition of PI3K/Akt and NF-kappaB. Biochem Pharmacol 2009 78 : 396 405.
40. Sousa LP, et al. PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3K/Akt-dependent and NF-κB-independent manner. J Leukoc Biol 2010 87 : 895 904.
41. Rossi AG, Hallett JM, Sawatzky DA, Teixeira MM, Haslett C. Modulation of granulocyte apoptosis can influence the resolution of inflammation. Biochem Soc Trans 2007 35 : 288 291.
42. Stephens L, Milne L, Hawkins P. Moving towards a better understanding of chemotaxis. Curr Biol 2008 18 : R485 R494.
43. Ferguson GJ, et al. PI(3)Kgamma has an important context-dependent role in neutrophil chemokinesis. Nat Cell Biol 2007 9 : 86 91.
44. Engelhardt B, Wolburg H. Mini-review: transendothelial migration of leukocytes: through the front door or around the side of the house? Eur J Immunol 2004 34 : 2955 2963.
45. Fernandez-Borja M, van Buul JD, Hordijk PL. The regulation of leukocyte transendothelial migration by endothelial signaling events. Cardiovasc Res 2010 86 : 202 210.
46. Buckley CD, et al. Identification of a phenotypically and functionally distinct population of long-lived neutrophils in a model of reverse endothelial migration. J Leukoc Biol 2006 79 : 303 311.
47. Martin C, Burdon PC, Bridger G, Gutierrez-Ramos JC, Williams TJ, Rankin SM. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 2003 19 : 583 593.
48. Furze RC, Rankin SM. The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse. FASEB J 2008 22 : 3111 3119.
49. Furze RC, Rankin SM. Neutrophil mobilization and clearance in the bone marrow. Immunology 2008 125 : 281 288.
50. Brinkmann V, Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol 2007 5 : 577 582.
51. Kroemer G, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 2009 16 : 3 11.
52. Sawatzky DA, Willoughby DA, Colville-Nash PR, Rossi AG. The involvement of the apoptosis-modulating proteins ERK 1/2, Bcl-xL and Bax in the resolution of acute inflammation in vivo. Am J Pathol 2006 168 : 33 41.
53. Weigert A, Jennewein C, Brune B. The liaison between apoptotic cells and macrophages - the end programs the beginning. Biol Chem 2009 390 : 379 390.
54. Michlewska S, Dransfield I, Megson IL, Rossi AG. Macrophage phagocytosis of apoptotic neutrophils is critically regulated by the opposing actions of pro-inflammatory and anti-inflammatory agents: key role for TNF-alpha. FASEB J 2009 23 : 844 854.
55. Bournazou I, et al. Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin. J Clin Invest 2009 119 : 20 32.
56. Rajakariar R, et al. Novel biphasic role for lymphocytes revealed during resolving inflammation. Blood 2008 111 : 4184 4192.
57. Navarro-Xavier RA, Newson J, Silveira VL, Farrow SN, Gilroy DW, Bystrom J. A new strategy for the identification of novel molecules with targeted proresolution of inflammation properties. J Immunol 2010 184 : 1516 1525.
58. Bystrom J, et al. Resolution-phase macrophages possess a unique inflammatory phenotype that is controlled by cAMP. Blood 2008 112 : 4117 4127.
59. Fadok VA, de CA, Daleke DL, Henson PM, Bratton DL. Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts. J Biol Chem 2001 276 : 1071 1077.
60. Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S. Identification of Tim4 as a phosphatidylserine receptor. Nature 2007 450 : 435 439.
61. Park D, et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 2007 450 : 430 434.
62. Park SY, et al. Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages. J Cell Sci 2009 122 : 3365 3373.
63. Stuart LM, Ezekowitz RA. Phagocytosis: elegant complexity. Immunity 2005 22 : 539 550.
64. Fadok VA, Chimini G. The phagocytosis of apoptotic cells. Semin Immunol 2001 13 : 365 372.
65. Fadok VA, Bratton DL, Henson PM. Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences. J Clin Invest 2001 108 : 957 962.
66. Borges VM, et al. TNFalpha inhibits apoptotic cell clearance in the lung, exacerbating acute inflammation. Am J Physiol Lung Cell Mol Physiol 2009 297 : L586 L595.
67. Rossi AG, McCutcheon JC, Roy N, Chilvers ER, Haslett C, Dransfield I. Regulation of macrophage phagocytosis of apoptotic cells by cAMP. J Immunol 1998 160 : 3562 3568.
68. Hart SP, Dougherty GJ, Haslett C, Dransfield I. CD44 regulates phagocytosis of apoptotic neutrophil granulocytes, but not apoptotic lymphocytes, by human macrophages. J Immunol 1997 159 : 919 925.
69. Liu Y, et al. Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes. J Immunol 1999 162 : 3639 3646.
70. Giles KM, Ross K, Rossi AG, Hotchin NA, Haslett C, Dransfield I. Glucocorticoid augmentation of macrophage capacity for phagocytosis of apoptotic cells is associated with reduced p130Cas expression, loss of paxillin/pyk2 phosphorylation, and high levels of active Rac. J Immunol 2001 167 : 976 986.
71. McColl A, Michlewska S, Dransfield I, Rossi AG. Effects of glucocorticoids on apoptosis and clearance of apoptotic cells. Sci World J 2007 7 : 1165 1181.
72. Ogden CA, et al. Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt's lymphoma. J Immunol 2005 174 : 3015 3023.
73. Xu W, Roos A, Schlagwein N, Woltman AM, Daha MR, van KC. IL-10-producing macrophages preferentially clear early apoptotic cells. Blood 2006 107 : 4930 4937.
74. Mitchell S, et al. Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo. J Am Soc Nephrol 2002 13 : 2497 2507.
75. Maderna P, Godson C. Lipoxins: resolutionary road. Br J Pharmacol 2009 158 : 947 959.
76. Fadok VA, McDonald PP, Bratton DL, Henson PM. Regulation of macrophage cytokine production by phagocytosis of apoptotic and post-apoptotic cells. Biochem Soc Trans 1998 26 : 653 656.
77. McDonald PP, Fadok VA, Bratton D, Henson PM. Transcriptional and translational regulation of inflammatory mediator production by endogenous TGF-beta in macrophages that have ingested apoptotic cells. J Immunol 1999 163 : 6164 6172.
78. Huynh ML, et al. Defective apoptotic cell phagocytosis attenuates prostaglandin E2 and 15-hydroxyeicosatetraenoic acid in severe asthma alveolar macrophages. Am J Respir Crit Care Med 2005 172 : 972 979.
79. Vandivier RW, et al. Impaired clearance of apoptotic cells from cystic fibrosis airways. Chest 2002 121 (Suppl 89S.
80. Vandivier RW, Henson PM, Douglas IS. Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease. Chest 2006 129 : 1673 1682.
81. Vandivier RW, et al. Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J Clin Invest 2002 109 : 661 670.
82. Lauber K, et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 2003 113 : 717 730.
83. Mueller RB, Sheriff A, Gaipl US, Wesselborg S, Lauber K. Attraction of phagocytes by apoptotic cells is mediated by lysophosphatidylcholine. Autoimmunity 2007 40 : 342 344.
84. Truman LA, et al. CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood 2008 112 : 5026 5036.
85. Bournazou I, Mackenzie KJ, Duffin R, Rossi AG, Gregory CD. Inhibition of eosinophil migration by lactoferrin. Immunol Cell Biol 2010 88 : 220 223.
86. Scannell M, et al. Annexin-1 and peptide derivatives are released by apoptotic cells and stimulate phagocytosis of apoptotic neutrophils by macrophages. J Immunol 2007 178 : 4595 4605.
87. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005 6 : 1191 1197.
88. Gilroy DW, Lawrence T, Perretti M, Rossi AG. Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov 2004 3 : 401 416.
89. El KD, et al. 15-epi-lipoxin A4 inhibits myeloperoxidase signaling and enhances resolution of acute lung injury. Am J Respir Crit Care Med 2009 180 : 311 319.
90. Scannell M, Maderna P. Lipoxins and annexin-1: resolution of inflammation and regulation of phagocytosis of apoptotic cells. Sci World J 2006 6 : 1555 1573.
91. Murray J, et al. Hypoxic regulation of neutrophil apoptosis role: of reactive oxygen intermediates in constitutive and tumor necrosis factor alpha-induced cell death. Ann NY Acad Sci 2003 1010 : 417 425.
92. Ward C, Walker A, Dransfield I, Haslett C, Rossi AG. Regulation of granulocyte apoptosis by NF-kappaB. Biochem Soc Trans 2004 32 : 465 467.
93. Villunger A, O'Reilly LA, Holler N, Adams J, Strasser A. Fas ligand, Bcl-2, granulocyte colony-stimulating factor, and p38 mitogen-activated protein kinase: regulators of distinct cell death and survival pathways in granulocytes. J Exp Med 2000 192 : 647 658.
94. Watson RW, et al. Regulation of Fas antibody induced neutrophil apoptosis is both caspase and mitochondrial dependent. FEBS Lett 1999 453 : 67 71.
95. Ward C, et al. NF-kappaB activation is a critical regulator of human granulocyte apoptosis in vitro. J Biol Chem 1999 274 : 4309 4318.
96. Allen L, et al. Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo. J Immunol 2005 174 : 3643 3649.
97. Usher LR, et al. Induction of neutrophil apoptosis by the Pseudomonas aeruginosa exotoxin pyocyanin: a potential mechanism of persistent infection. J Immunol 2002 168 : 1861 1868.
98. Lee A, Whyte MK, Haslett C. Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol 1993 54 : 283 288.
99. Rossi AG, Cousin JM, Dransfield I, Lawson MF, Chilvers ER, Haslett C. Agents that elevate cAMP inhibit human neutrophil apoptosis. Biochem Biophys Res Commun 1995 217 : 892 899.
100. Martin MC, Dransfield I, Haslett C, Rossi AG. Cyclic AMP regulation of neutrophil apoptosis occurs via a novel protein kinase A-independent signaling pathway. J Biol Chem 2001 276 : 45041 45050.
101. Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol 1995 154 : 4719 4725.
102. Meagher LC, Cousin JM, Seckl JR, Haslett C. Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 1996 156 : 4422 4428.
103. Hannah S, Nadra I, Dransfield I, Pryde JG, Rossi AG, Haslett C. Constitutive neutrophil apoptosis in culture is modulated by cell density independently of beta2 integrin-mediated adhesion. FEBS Lett 1998 421 : 141 146.
104. Hannah S, et al. Hypoxia prolongs neutrophil survival in vitro. FEBS Lett 1995 372 : 233 237.
105. Mecklenburgh KI, et al. Involvement of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis. Blood 2002 100 : 3008 3016.
106. Pryde JG, Walker A, Rossi AG, Hannah S, Haslett C. Temperature-dependent arrest of neutrophil apoptosis. Failure of Bax insertion into mitochondria at 15 degrees C prevents the release of cytochrome c. J Biol Chem 2000 275 : 33574 33584.
107. Stern M, Meagher L, Savill J, Haslett C. Apoptosis in human eosinophils. Programmed cell death in the eosinophil leads to phagocytosis by macrophages and is modulated by IL-5. J Immunol 1992 148 : 3543 3549.
108. Falcone FH, Zillikens D, Gibbs BF. The 21st century renaissance of the basophil? Current insights into its role in allergic responses and innate immunity Exp Dermatol 2006 15 : 855 864.
109. Yoshimura C, et al. Glucocorticoids induce basophil apoptosis. J Allergy Clin Immunol 2001 108 : 215 220.
110. Matsumoto K, Maeda A, Bochner BS, Wakiguchi H, Saito H. Induction of apoptosis in human basophils by anti-Fas antibody treatment in vitro. Int Arch Allergy Immunol 2008 146 (Suppl 40 46.
111. Kawakami A, et al. Enhancement of basophil apoptosis by olopatadine and theophylline. Allergy Asthma Proc 2008 29 : 322 328.
112. Kawakami T, Galli SJ. Regulation of mast-cell and basophil function and survival by IgE. Nat Rev Immunol 2002 2 : 773 786.
113. Krauth MT, et al. Effects of the CD33-targeted drug gemtuzumab ozogamicin (Mylotarg) on growth and mediator secretion in human mast cells and blood basophils. Exp Hematol 2007 35 : 108 116.
114. Heinemann A, et al. Stem cell factor stimulates the chemotaxis, integrin upregulation, and survival of human basophils. J Allergy Clin Immunol 2005 116 : 820 826.
115. Zheng X, et al. Interleukin-3, but not granulocyte-macrophage colony-stimulating factor and interleukin-5, inhibits apoptosis of human basophils through phosphatidylinositol 3-kinase: requirement of NF-kappaB-dependent and -independent pathways. Immunology 2002 107 : 306 315.
116. Didichenko SA, Spiegl N, Brunner T, Dahinden CA. IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils. Blood 2008 112 : 3949 3958.
117. Cabrini M, Nahmod K, Geffner J. New insights into the mechanisms controlling neutrophil survival. Curr Opin Hematol 2010 17 : 31 35.
118. Pinho V, et al. Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation. J Leukoc Biol 2005 77 : 800 810.
119. Pinho V, et al. Tissue- and stimulus-dependent role of phosphatidylinositol 3-kinase isoforms for neutrophil recruitment induced by chemoattractants in vivo. J Immunol 2007 179 : 7891 7898.
120. Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 2007 25 : 101 137.
121. Feldmann M, Maini RN. Discovery of TNF-alpha as a therapeutic target in rheumatoid arthritis: preclinical and clinical studies. Joint Bone Spine 2002 69 : 12 18.
122. Barros TP, Alderton WK, Reynolds HM, Roach AG, Berghmans S. Zebrafish: an emerging technology for in vivo pharmacological assessment to identify potential safety liabilities in early drug discovery. Br J Pharmacol 2008 154 : 1400 1413.
123. Renshaw SA, Loynes CA, Trushell DM, Elworthy S, Ingham PW, Whyte MK. A transgenic zebrafish model of neutrophilic inflammation. Blood 2006 108 : 3976 3978.
124. Renshaw SA, Loynes CA, Elworthy S, Ingham PW, Whyte MK. Modeling inflammation in the zebrafish: how a fish can help us understand lung disease. Exp Lung Res 2007 33 : 549 554.
125. Koedel U, et al. Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal meningitis. PLoS Pathog 2009 5 : e1000461.
126. Jones HA, Clark RJ, Rhodes CG, Schofield JB, Krausz T, Haslett C. In-vivo measurement of neutrophil activity in experimental lung inflammation. Am J Respir Crit Care Med 1994 149 : 1635 1639.
127. Breckwoldt MO, et al. Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci USA 2008 105 : 18584 18589.
128. Cortez-Retamozo V, et al. Real-time assessment of inflammation and treatment response in a mouse model of allergic airway inflammation. J Clin Invest 2008 118 : 4058 4066.
129. Li HN, et al. Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL-37 is not proinflammatory to phagocytosing macrophages. J Leukoc Biol 2009 86 : 891 902.
130. Miles K, et al. Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol 2009 183 : 2122 2132.
131. Lloberas J, Celada A. p21(waf1/CIP1), a CDK inhibitor and a negative feedback system that controls macrophage activation. Eur J Immunol 2009 39 : 691 694.
132. Scatizzi JC, et al. The CDK domain of p21 is a suppressor of IL-1beta-mediated inflammation in activated macrophages. Eur J Immunol 2009 39 : 820 825.
133. Ren Y, et al. Apoptotic cells protect mice against lipopolysaccharide- induced shock. J Immunol 2008 180 : 4978 4985.
134. McColl A, et al. Glucocorticoids induce protein S-dependent phagocytosis of apoptotic neutrophils by human macrophages. J Immunol 2009 183 : 2167 2175.