Ligation of intercellular adhesion molecule 3 induces apoptosis of human blood eosinophils and neutrophils.
BACKGROUND
Intercellular adhesion molecule 3 (ICAM-3) is highly expressed on human granulocytes, including eosinophils and neutrophils, but the functions of ICAM-3 in these cells are not well understood.


OBJECTIVE
Our studies test the hypothesis that ICAM-3 regulates granulocyte apoptosis.


METHODS
Intercellular adhesion molecule 3 was activated by a mAb that recognizes an ICAM-3 epitope that binds its ligand, CD11a/CD18. In some experiments with eosinophils, recombinant human IL-5 or GM-CSF was added to mimic in vivo antiapoptotic conditions. Staining with annexin V-fluorescein isothiocyanate and propidium iodide identified apoptotic cells.


RESULTS
Binding of ICAM-3 increased apoptosis of both eosinophils (18 and 48 hours) and neutrophils (18 hours). At 18 hours, eosinophil apoptosis increased from 31.4% +/- 3.5 SE (IgG control) to 45.2% +/- 3.8 SE (anti-ICAM-3), and neutrophil apoptosis increased from 48% +/- 4.1 SE (IgG control) to 55.3% +/- 4.5 SE (anti-ICAM-3). At 48 hours, eosinophil apoptosis increased 2-fold under baseline conditions and also in the presence of recombinant human IL-5 or GM-CSF. In both eosinophils and neutrophils, incubation with a blocking antibody against CD18 integrins blunted ICAM-3-induced apoptosis. In eosinophils, blocking peptides for caspases 8 and 9, proteases critical to apoptosis, also decreased ICAM-3-induced apoptosis to control levels.


CONCLUSIONS
Through its effect on eosinophil and neutrophil apoptosis, ICAM-3 may be an important anti-inflammatory molecule that can oppose the proinflammatory effects of IL-5 and GM-CSF.


CONCLUSIONS
These findings provide a mechanism for apoptotic clearance of eosinophils and neutrophils involved in allergic inflammation that, unlike necrosis, does not cause nonspecific tissue injury.
Kessel
Julie M
JM
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, WI 53715, USA. jmkessel@wisc.edu
Sedgwick
Julie B
JB
Busse
William W
WW
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology*; D018821:CD18 Antigens / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004789:Enzyme Activation / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D053148:Caspase 3