Modulation of human neutrophil effector functions by monoclonal antibodies against surface membrane molecules of 94,000 and 180,000 molecular weight

Abstract

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.