In situ activation of murine peritoneal macrophages by cyclohexyl-1,3-dioxepin and 4-methyl-2-pentenoyl maleic anhydride copolymers.

Peritoneal macrophages (PM theta) from mice treated intraperitoneally with the unique polyanionic compounds cyclohexyl-1,3-dioxepin maleic anhydride copolymer (CDA-MA) and 4-methyl-2-pentenoyl maleic anhydride copolymer (MP-MA) had tumoricidal activity against Lewis lung tumor cells. 5'-Nucleotidase ectoenzyme activity, which had previously been associated only with nontumoricidal, resident PM theta, was elevated in tumoricidal PM theta elicited with CDA-MA and MP-MA. Cell counts and differentials performed on peripheral blood leukocytes and PM theta populations from CDA-MA- and MP-MA--treated mice more closely corresponded to those of normal mice than mice treated with the conventional PM theta-activating agents pyran and Corynebacterium parvum. In addition, the lysosomal peroxidase activity in PM theta after administration of CDA-MA and MP-MA remained at levels comparable with normal resident PM theta, while an influx of peroxidase-positive macrophages was observed after administration of pyran and C. parvum. Inoculation of CDA-MA and MP-MA into mice bearing Lewis lung carcinoma showed a significant increase in median survival time compared with control mice, as well as an increase in the percentage of mice that survived greater than 90 days. Taken together, these data suggest that CDA-MA and MP-MA activated PM theta in situ and prolonged survival against primary transplanted Lewis lung carcinoma.