Synergism between human monocyte chemotactic and activating factor and bacterial products for activation of tumoricidal properties in murine macrophages

Chemotactic factors regulate the recruitment of monocytes-macrophages to inflammatory sites and neoplastic tissues. The purpose of this study was to determine whether MCAF also influences the activation of C3H/HeN macrophages to become tumoricidal. Several metastatic and nonmetastatic clones of the K-1735 murine melanoma cells syngeneic to C3H/HeN mice were transfected with expression vectors containing the human MCAF gene or control DNA. Tumor cells producing high levels of MCAF were significantly lysed by macrophages treated with IPS, whereas parental or control transfected cells were not. Control-activated macrophages incubated with both IFN-γ and IPS lysed all the melanoma cells regardless of MCAF production. Pretreatment of macrophages with MCAF significantly enhanced their response to low concentrations of LPS, muramyl tripeptide, and a synthetic bacterial LPP, as measured by lysis of murine melanoma cells. These data suggest that in addition to being a chemotactic factor, MCAF can prime macrophages to respond to endotoxins and other bacterial products and therefore may regulate several levels of macrophage-tumor interactions in situ.