A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation.
In mice selectively deficient in CD11b/CD18, a beta 2 integrin, chemoattractant-induced leukocyte adhesion to microvascular endothelium in vivo was reduced. Paradoxically, thioglycollate-induced neutrophil accumulation in the peritoneal cavity was increased and was associated with a significant delay in apoptosis of extravasated cells. The extravasated cells had a near absence of neutrophil phagocytosis and a reduction in oxygen free radical generation, which may contribute to the observed defect in apoptosis. This is supported by our in vitro studies, in which phagocytosis of opsonized particles by human neutrophils rapidly induced apoptosis that could be blocked with CD11b/ CD18 antibodies. Reactive oxygen species are the intracellular link in this process: phagocytosis-induced apoptosis was blocked both in neutrophils treated with the flavoprotein inhibitor diphenylene iodonium and in neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase. Thus, CD11b/CD18 plays a novel and unsuspected homeostatic role in inflammation by accelerating the programmed elimination of extravasated neutrophils.
Coxon
A
A
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Rieu
P
P
Barkalow
F J
FJ
Askari
S
S
Sharpe
A H
AH
von Andrian
U H
UH
Arnaout
M A
MA
Mayadas
T N
TN
D000818:Animals; D017209:Apoptosis; D001772:Blood Cell Count; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism*; D006105:Granulomatous Disease, Chronic / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D018448:Models, Immunological; D019255:NADPH Oxidases; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology; D010587:Phagocytosis; D017382:Reactive Oxygen Species; D016897:Respiratory Burst; D013864:Thioglycolates / Q000494:pharmacology
D018821:CD18 Antigens; D016023:Integrins; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D017382:Reactive Oxygen Species; D013864:Thioglycolates; D019255:NADPH Oxidases