Secretion of antimycobacterial fatty acids by normal and activated macrophages

Cellular resistance to facultative intracellular parasites has been studied by determining the antimycobacterial activity and the amount of fatty acids in sera and in heptane extracts of freshly collected and 24-h-cultured normal and activated guinea pig alveolar macrophages and liver cells. The quantity and the antimycobacterial activity of extractable fatty acids were determined by gas chromatography and the agar plate diffusion test, respectively. These determinations showed that heptane extracts of activated cells inhibited the growth of BCG much more effectively than fractions prepared from normal cells; chromatographic analyses showed that extracts of activated cells contained six times more C(16) and C(18) long-chain fatty acids than did fractions of normal cells. Heptane extracts of 24-h-cultured cells and of their media showed that during incubation normal and activated cells release fatty acids into the culture media without apparent cell injury; in all experiments liver cells produced larger amounts of fatty acids than alveolar macrophages. Sera collected from activated guinea pigs inhibited the growth of BCG and contained two to five times more total fatty acids than did the growth-supporting normal serum. That bactericidal fatty acids are excreted into the tissue culture medium of incubated cells or into the blood of immunologically stimulated animals suggests that macrophages can exert antibacterial effects without phagocytosis.