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Department of Medicine, UCLA-VA Wadsworth Medical Center and the Jonsson Comprehensive Cancer Center, Los Angeles, California 90073
Murine peritoneal neutrophils (PMNs), elicited by i.p. injection of formalin-killed Corynebacteria parvum, spontaneously lyse teratocarcinoma targets through the secretion of reactive oxygen intermediates. Examination of effector-target interactions at the single cell level revealed that PMNs conjugated to tumor cells were 3-fold more frequently stained by nitroblue tetrazolium compared to nonconjugating PMNs suggesting that tumor targets stimulated a potent tumor-lytic respiratory burst. This notion was confirmed by the detection of superoxide and hydrogen peroxide generation from PMNs as well as a luminol-dependent chemiluminescent response following conjugation with viable tumor targets. Generation of superoxide was dependent upon the presence of dihydrocytochalasin B. In addition to teratocarcinoma cells, comparable stimulation was achieved by conjugation with YAC and P815 targets but not thymocytes. Reactive oxygen intermediate release was also achieved by mixing peritoneal PMNs with heat-killed tumor cells. In contrast to bacteria-induced effectors, PMNs elicited by i.p. injection of thioglycollate were incapable of responding following conjugation with tumor targets although they were competent for reactive oxygen intermediate release when stimulated by phorbol myristate acetate. Teratocarcinoma targets were sensitive to concentrations of H2O2 that could be achieved by PMNs following contact. These data indicate that Corynebacteria-elicited inflammatory PMNs lyse their bound tumor targets by a mechanism similar to a stimulus-secretion model.
1 Supported by USPHS Grant R01-CA37184-01A1, National Cancer Institute, Department of Health and Human Services, and research funds of the Veteran's Administration.
2 To whom requests for reprints should be addressed, at VA Wadsworth Hospital, 691/111H, Wilshire and Sawtelle Boulevards, Los Angeles, CA 90073.
Received 10/30/86. Revised 1/30/87. Accepted 2/ 5/87.
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