Procoagulant activity of macrophages associated with different murine neoplasms

Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of human and experimental tumors, might contribute to tumor-associated fibrin deposition through the development of procoagulant activity (PCA). We have investigated PCA of tumor-associated macrophages (TAM) in 6 transplanted murine tumors in syngeneic hosts; peritoneal macrophages from tumor-bearing and control animals were studied also, as reference cell populations. PCA was evaluated by a one-stage clotting assay immediately after preparation and following incubation in the absence and in the presence of endotoxin. TAM from 5 poorly immunogenic tumors (mFS6, MN/MCA1, R 80/44, M109 and MS2) had basal PCA levels comparable to or somewhat lower than those of peritoneal macrophages from the same animals. Similar PCA was found in peritoneal macrophages from both control and tumor-bearing animals. Unlike peritoneal macrophages, TAM in all instances failed to respond with increased PCA when exposed to endotoxin in vitro. Failure to respond to endotoxin could not be ascribed to contaminating tumor cells or their products, to the presence of suppressive macrophage populations or to the lack of lymphocyte "help". TAM from a strongly immunogenic, regressing tumor (MSV sarcoma), in contrast to its non-immunogenic variant, MS2, and to the 4 other tumors mentioned above, expressed high levels of PCA immediately after isolation. The latter did not increase further following in vitro stimulation with endotoxin. When MSV sarcomas were induced in nude mice, TAM showed PCA levels similar to those of the euthymic hosts, suggesting that the procoagulant response was largely independent of T-cell-mediated immunity.