Modulation of human neutrophil effector functions by monoclonal antibodies against surface membrane molecules of 94,000 and 180,000 molecular weight.
Function-related antigens on the neutrophil (PMN) surface were identified using two newly developed PMN-specific mouse monoclonal antibodies. These IgG antibodies, designated Ab 1-14 and Ab 1-15, were selected for detailed study after initial testing revealed their significant inhibition of PMN superoxide generation in response to N-formyl-Met-Leu-Phe (FMLP) (64% for 1-14 and 64% for 1-15; P less than .05). In further experiments, Ab 1-14 augmented PMN adhesion (by 111%; P less than .01) and degranulation (by 52%; P less than .05) in response to FMLP, while Ab 1-15 inhibited these responses by 42% and 29%, respectively (P less than .05). Ab 1-14 reduced PMN chemotaxis in response to FMLP by 37% (P less than .02), and unlike Ab 1-15, Ab 1-14 significantly reduced unstimulated PMN binding of complement-coated sheep red blood cells. Ab 1-14 and Ab 1-15 significantly reduced PMN superoxide production in response to phorbol myristate acetate (PMA) (14% and 23%, respectively; P less than .05). Whereas 1-14 was found to increase PMA-induced cell degranulation significantly (175%), Ab 1-15 did not alter degranulation response to PMA. Immunoprecipitation showed that Ab 1-14 and Ab 1-15 recognized respective surface antigens of 94,000 mol wt and 130,000 to 180,000 mol wt. Our findings suggest that the surface molecules identified by these two monoclonal antibodies play a significant role in neutrophil activation by both FMLP and PMA.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology*; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate