TUMORICIDAL RESPONSE OF LIVER MACROPHAGES ISOLATED FROM RATS BEARING LIVER METASTASES OF COLON ADENOCARCINOMA

Intraportal inoculation of CC531 adenocarcinoma cells into syngeneic r ats causes an increase of liver macrophage cell number but not of majo r histocompatibility complex class II antigen expression. On day I aft er inoculation of 10(5) CC531 cells, a fixed number of isolated liver macrophages lysed significantly more target cells in vitro than did co ntrol cells, This effect was still present after 4 weeks. A 10-fold hi gher initial tumor dose significantly suppressed the macrophage respon se during the first 2 weeks. In contrast to tumoricidal activity induc ed by lipopolysaccharide in vitro, the tumoricidal response following in vivo challenge with tumor cells appeared not closely related to the production of reactive nitrogen intermediates, as in the latter case it was not abrogated in the presence of nitric oxide synthase inhibito r. Furthermore, the liver macrophage population appeared not fully act ivated after tumor inoculation as lipopolysaccharide further increased tumoricidal activity in vitro, The observed numerical and functional response of liver macrophages to intraportally inoculated tumor cells points at an important role of these cells in aspecific immune reactiv ity aimed at the reduction of local tumor growth, Results suggest that mechanistic differences exist between macrophage tumoricidal activity induced by tumor cells as compared with lipopolysaccharide.