HYALURONAN SYNTHESIS BY RAT-LIVER STELLATE CELLS IS ENHANCED UNDER ENDOTOXIC CONDITIONS

As part of an investigation of the effect of sepsis on the sinusoidal cells of liver we studied the influence of conditioned media from Kupffer cells (KC) and liver endothelial cells (LEC) from normal rats and animals pretreated with endotoxin (ET) on the hyaluronan (HA) production by stellate cells (SC) in culture. SC proliferation, as measured by direct cell counting and [H-3]-thymidine incorporation, was also recorded. An SC from an ET-treated rat produces similar amounts of HA as a normal SC when grown in culture medium containing 10% fetal calf serum (FCS). When animals were treated with ET, there was, however, an increase in the yield of isolated SC and thus the whole cell population in ET-treated rats has a potential to produce a larger amount of the polysaccharide. Factors present particularly in the KC conditioned media supplemented with 10% FCS from normal and endotoxemic animals greatly stimulated the proliferation and synthesis of HA in SC cultures, after a lag-phase which was four days for normal SC and three days from ET-treated animals. The rate of HA synthesis was closely related to the increase in the amount of thymidine incorporation into DNA. Conditioned media containing 1 0 % FCS obtained from LEC cultures were also stimulatory but were less effective in inducing cell proliferation and production of HA. We suggest that the elevation of plasma HA found in severe endotoxemia and sepsis may be caused in part by the: (i) increased numer of SC; (ii) an in vivo activation of SC population which predisposes for HA-production; and, (iii) action of factors or mediators from cells of the reticuloendothelial system of the liver on the cell proliferation and on the HA synthesis in the SC population.