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CH King, CA Peck, CS Haimes, JW Kazura, PJ Spagnuolo, JA Sawyer, GR Olds and AA Mahmoud
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.
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