HETEROGENEITY IN SECRETORY RESPONSES OF RAT-LIVER MACROPHAGES OF DIFFERENT SIZE

Four subpopulations of hepatic macrophages, differing in size, were is olated from rat liver. The secretion of nitric oxide (NO), tumor necro sis 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 macroph ages could be induced to secrete significant levels of NO, TNF-alpha, PGE and IL-1. The extent of secretion, however, varied substantially b etween macrophages of different size. The highest levels of secretion of TNF-alpha, PGE and IL-1 were observed in the fraction containing th e large-size macrophages, while progressively lower levels of secretio n were observed with decreasing size. In constrast, the highest levels of NO secretion were observed by small macrophages and steadily decre ased with increasing size. Hepatic macrophages of different size displ ayed differences in secretory potential during in vitro culture. The a bility of small liver macrophages to secrete NO, TNF-alpha, or PGE, fo llowing activation with MDP, gradually increased with time in culture. In contrast, large liver macrophages gradually lost their secretory a bility after 1-2 days and the intermedicate-size cells after 2-3 days in culture. This functional heterogeneity in secretory properties amon g rat liver macrophages of different size is discussed with reference to their potential role and significance in host defense against metas tatic tumor growth in the liver.