Inhibition of zymosan activation of human neutrophil oxidative metabolism by a mouse monoclonal antibody

Abstract

We have studied a neutrophil-specific murine monoclonal antibody, PMN7C3 (IgG3), which specifically alters PMN oxidative metabolism stimulated by serum-opsonized zymosan (STZ) or Candida albicans (STC). Polymorphonclear cells (PMNs) exposed to PMN7C3 shows a significant depression in O2- release (52.8% ± 2.5% of control), H2O2 release (44.4% ± 6.0% of control), and O2 consumption (73.9% ± 2.6% of control) in response to STZ. O2- release in response to phorbol myristate acetate (PMA) was modestly reduced (78.4% ± 3.7%) by PMN7C3 treatment, but not to the extent seen with STZ or STC. PMN7C3 did not affect O2- release by PMNs stimulated by zymosan opsonized with IgG or by S. aureus, A 23187, or FMLP. PMN7C3 was not cytotoxic, did not trigger oxidative metabolism when used as a stimulus, did not alter STZ-induced degranulation, and did not interfere with binding or uptake of STZ by PMNs. Exposure of PMNs to PMN7C3 decreased PMN rosette formation with erythrocytes coated with C3b (54% of control) or C3bi (63% of control), but had no affect on rosette formation with IgG-coated erythrocytes. PMN7C3 does not bind to monocytes and had no affect on rosette formation by this cell type. Binding of antibody PMN7C3 to the neutrophil surface inhibits the oxidative response to opsonized STZ or STC, possibly in part by altering the function or expression of C3b and C3bi receptors. Monoclonal antibodies such as PMN7C3 provide highly specific probes that might be used to define the molecular features of the stimulus-coupled response of PMN activation.