EFFECT OF INOCULATION WITH NEURAMINIDASE-TREATED TUMOR-CELLS ON MACROPHAGE CYTOTOXICITY INVITRO

Adherent peritoneal exudate cells (PM) and macrophages isolated from tumor tissue from C57BL/6J .times. DBA/2J F1 mice previously inoculated with tumor cells treated with Vibrio cholerae neuraminidase and mitomycin C were studied for their cytotoxic effect on established tumor cell monolayers by time-lapse cinematography. The 2 murine pulmonary tumors studied were the spontaneous Lewis lung tumor and a 3-methylcholanthrene-induced squamous cell carcinoma. Tumor cells incubated alone, with PM from untreated mice and with macrophages isolated from tumor tissue from untreated or treated mice grew to confluence by 24 h of coincubation and displayed no observable detrimental change by 96 h. Cytotoxic PM were isolated from tumor-bearing mice that received a s.c. inoculation of tumor cells treated with V. cholerae neuraminidase and mitomycin C and from tumor-free animals inoculated i.p. with tumor cells treated simultaneously with V. cholerae neuraminidase and mitomycin C, or administered tumor cells treated with mitomycin C alone. PM isolated from mice within 3 days of inoculation with treated tumor cells killed cultures of the identical tumor by 36 h, but they did not kill cultures of another tumor until 48 h of coincubation. If PM were isolated 18 days following the final inoculation of treated tumor cells, they killed cultures of the same tumor by 36 h, but they had no cytotoxic effect upon those of another tumor. PM from mice treated with BCG or BCG cell walls killed tumor cells in culture by 48 h. Apparently specifically cytotoxic macrophages kill tumor cells by 36 h, whereas nonspecificially cytotoxic macrophages do not kill until 48 h of coincubation.