Activation of human neutrophil LFA-1 (CD11a) by leukotriene B4.
Homotypic aggregation (HA) of human neutrophils by the potent leukotactic factor, leukotriene B4 (LTB4), and phorbol myristate acetate (PMA) was evaluated by recording the net decrease in absorbency at 650 nm of suspensions of 10(7) neutrophils/ml in a microtiter plate reader, which was found to correlate with microscopic evidence of aggregation. LTB4-elicited HA was increased maximally by approximately one third above HA in buffer at 30 min, whereas PMA-induced HA reached a maximal level more than 2 1/2-fold higher than buffer control at 60 min. The involvement of LFA-1 in LTB4-induced HA of neutrophils was suggested initially by the inhibitory effect of monoclonal anti-CD18 and anti-CD11a antibodies. The binding to neutrophils of a monoclonal anti-LFA-1 antibody (NK1-L16) specific for an activation epitope of CD11a was increased a maximum of 28-fold and sixfold, respectively, after 1 and 5 min of preincubation with 10 nM LTB4 and fivefold after 5 min with PMA. Thus, both LTB4 and PMA induce an activating conformational change in the CD11a adherence receptor of human neutrophils.
Shames
R S
RS
Department of Medicine, University of California Medical Center, San Francisco 94143-0724.
Goetzl
E J
EJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D007975:Leukotriene B4; D013755:Tetradecanoylphorbol Acetate