CD50 monoclonal antibodies inhibit neutrophil activation.
The constitutive high expression of CD50 (ICAM-3) on resting leukocytes, coupled with the observation that CD50 is the primary LFA-1 ligand on resting T cells, suggests that CD50 may be an important LFA-1 ligand in the initiation of the immune/inflammatory response. CD50 mAbs have been reported to increase homotypic adhesion of lymphocytes, and lymphocyte adhesion to HUVEC and extracellular matrix proteins. In this study, the effects of CD50 mAbs on neutrophil activation were examined. CD50 mAbs were found to inhibit neutrophil adhesion induced by FMLP and 12-O-tetradecanoyl-phorbol-13-acetate to resting and TNF-activated HUVEC. CD50 mAbs also inhibited neutrophil adhesion stimulated by CD66a, CD66b, CD66c, and CD66d mAbs to HUVEC. CD50 mAbs inhibited the up-regulation of CD11b/CD18 to the neutrophil surface, and the down-regulation of surface CD62L expression. The potential contribution of src family kinases to the previously described tyrosine kinase activity associated with CD50 in neutrophils was also examined. hck and lyn were found to account for much of the tyrosine kinase activity associated with CD50 in neutrophils. The data indicate that CD50 in neutrophils functions not only as a potential ligand for LFA-1, but also regulates the surface expression and activity of CD11b/CD18 and CD62L. In contrast to the effects in lymphocytes, CD50 appears to function as a negative regulator of neutrophil activation.
Skubitz
K M
KM
Department of Medicine, The University of Minnesota Medical School, and Masonic Cancer Center, Minneapolis, 55455, USA.
Campbell
K D
KD
Skubitz
A P
AP
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D019041:L-Selectin / Q000276:immunology; D018375:Neutrophil Activation / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D019041:L-Selectin