Ligation of intercellular adhesion molecule 3 induces apoptosis of human blood eosinophils and neutrophils - 16/08/11
, Julie B. Sedgwick, PhD b, William W. Busse, MD b
Reprint requests: Julie M. Kessel, MD, Department of Pediatrics, Division of Neonatology, University of Wisconsin and Meriter Hospital, 202 South Park Street, 6 Center, Madison, WI 53715.Madison, Wis
Abstract |
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.
Conclusion |
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.
Clinical implications |
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.
Le texte complet de cet article est disponible en PDF.Key words : ICAM-3, adhesion molecules, neutrophils, eosinophils, apoptosis
Abbreviations used : FITC, FMK, ICAM, PI
Plan
| Supported by the University of Wisconsin Medical School and National Institutes of Health grant K08-A145923. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 118 - N° 4
P. 831-836 - octobre 2006 Retour au numéro
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