CD50 MONOCLONAL-ANTIBODIES INHIBIT NEUTROPHIL ACTIVATION

The constitutive high expression of CD50 (ICAM-3) on resting leukocyte s, 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 ligan d in the initiation of the immune/inflammatory response, CD50 mAbs hav e been reported to increase homotypic adhesion of lymphocytes, and lym phocyte adhesion to HUVEC and extracellular matrix proteins, In this s tudy, the effects of CD50 mAbs on neutrophil activation were examined, CD50 mAbs were found to inhibit neutrophil adhesion induced by FMLP a nd 12-O-tetradecanoyl-phorbol-13-acetate to resting and TNF-activated HUVEC, CD50 mAbs also inhibited neutrophil adhesion stimulated by CD66 a, CD66b, CD66c, and CD66d mAbs to HUVEC, CD50 mAbs inhibited the up-r egulation of CD11b/CD18 to the neutrophil surface, and the downregulat ion of surface CD62L expression, The potential contribution of src fam ily kinases to the previously described tyrosine kinase activity assoc iated with CD50 in neutrophils was also examined, hck and lyn were fou nd to account for much of the tyrosine kinase activity associated with CD50 in neutrophils. The data indicate that CD50 in neutrophils funct ions not only as a potential ligand for LFA-1, but also regulates the surface expression and activity of CD11b/CD18 and CD62L, In contrast t o the effects in lymphocytes, CD50 appears to function as a negative r egulator of neutrophil activation.