Ligation of members of the beta 1 or the beta 2 subfamilies of integrins by antibodies triggers eosinophil respiratory burst and spreading.
Eosinophils interact with extracellular matrix proteins and endothelial cells through adhesion proteins belonging to the beta 1 and beta 2 subfamilies of integrins. Extending previous observations, we found that tumour necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor stimulated generation of superoxide anion by eosinophils plated on fibronectin-coated surfaces. As studies with adherent neutrophils indicated that TNF might act as activating leucocyte integrins to deliver signals involved in activation of cell functions, we investigated the effects of monoclonal antibodies (mAb) directed against VLA-4 (CD49d/CD29), LFA-1 (CD11a/CD18), CR3 (CD11b/CD18) or the common beta 2 subunit (CD18) on generation of eosinophil toxic oxygen molecules and spreading. We show that cross-linking of members of both the beta 1 and the beta 2 integrin subfamilies triggers eosinophil respiratory burst and spreading. Evidence for the selectivity of anti-integrin mAb effects is derived from the findings that isotype-matched mAb of other specificities (anti-class I MHC Ag, anti-beta 2-microglobulin, anti-CD4) did not trigger eosinophil functions. The findings presented in this paper suggest that integrin-dependent, eosinophil adhesion in sites of allergic reaction may be accompanied by release of toxic oxygen molecules involved in tissue damage.
Laudanna
C
C
Institute of General Pathology, University of Verona, Italy.
Melotti
P
P
Bonizzato
C
C
Piacentini
G
G
Boner
A
A
Serra
M C
MC
Berton
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains; D016023:Integrins / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016029:Receptors, Very Late Antigen / Q000276:immunology; D016897:Respiratory Burst / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; C063493:CDw49d; D039001:Integrin alpha Chains; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen