Heterogeneity in secretory responses of rat liver macrophages of different size

Four subpopulations of hepatic macrophages, differing in size, were isolated from rat liver. The secretion of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E (PGE) and interleukin-1 (IL-1) by freshly isolated as well as cultured cells was studied after in vitro stimulation with the immunomodulator muramyl dipeptide (MDP) in free or liposome-encapsulated form. Freshly isolated liver macrophages could be induced to secrete significant levels of NO, TNF-alpha, PGE and IL-1. The extent of secretion, however, varied substantially between macrophages of different size. The highest levels of secretion of TNF-alpha, PGE and IL-1 were observed in the fraction containing the large-size macrophages, while progressively lower levels of secretion were observed with decreasing size. In constrast, the highest levels of NO secretion were observed by small macrophages and steadily decreased with increasing size. Hepatic macrophages of different size displayed differences in secretory potential during in vitro culture. The ability of small liver macrophages to secrete NO, TNF-alpha, or PGE, following activation with MDP, gradually increased with time in culture. In contrast, large liver macrophages gradually lost their secretory ability after 1-2 days and the intermedicate-size cells after 2-3 days in culture. This functional heterogeneity in secretory properties among rat liver macrophages of different size is discussed with reference to their potential role and significance in host defense against metastatic tumor growth in the liver.