Anti-tumor effect of inflammatory neutrophils: characteristics of in vivo generation and in vitro tumor cell lysis.

Inflammatory neutrophils elicited by intraperitoneal injection of Corynebacterium parvum, thioglycollate or proteose peptone were capable of lysing different murine and human tumor targets in a short-term chromium-release assay. A single-cell cytotoxicity assay, which evaluated effector-target cell interactions at the single-cell level, confirmed a PMN-mediated tumor-lytic effect. Optimal lysis was achieved by PMNs obtained 6 hr after injection of C. parvum and 16 hr after injection of thioglycollate. In vitro, loss of tumor cell membrane integrity occurred extremely rapidly following conjugation with inflammatory PMNs (beginning within 15 min of the binding step). By 45 min, the lytic event was completed. Addition of catalase or superoxide dismutase to the cytotoxicity assays prevented tumor lysis in a concentration-dependent fashion, indicating that hydrogen peroxide and superoxide, products of the PMN respiratory burst, are mediators of the lytic reaction.