The glycosaminoglycans in cultures of stimulated rat peritoneal macrophages. 1. Pattern and biosynthesis of glycosaminoglycans.

Macrophages produce and secrete proteoglycans. They are involved in inflammation and may contribute to the glycosaminoglycans (GAG) and proteoglycans (PG) characteristic of the inflamed area. This possible contribution was studied with rat peritoneal macrophages (pMP) in vitro. The total amount, composition, and neosynthesis of the GAG (as the main constituents of PG) were determined in cultured pMP of normal rats or rats pretreated with casein, BCG, thioglycolate or carrageenan. Partly the stimulated pMP were further activated with LPS or PMA. The rat pMP contained non-sulfated GAG, chondroitin sulfate and heparan sulfate but no dermatan sulfate. The GAG amount per cell increased with duration of the culture. In most cases the final level of GAG roughly corresponded to that of 12 micrograms hexuronic acid per 10(6) cells. It was lower after BCG stimulation (25%) and higher in pMP stimulated by both casein and LPS (200%). The average percentage of the GAG secreted (40%) was enhanced with pMP stimulated by carrageenan (87%) or casein plus LPS (69%). The pattern of the GAG in cultural media, cell coat and cells differed markedly. Thus the cell coat contained a higher amount of heparan sulfate. Differences due to stimulation were mainly seen in the reduced sulfation of the CS-proteoglycan secreted (casein-, BCG-pMP). According to studies on the incorporation of 35S-sulfate and 3H-acetate the GAG of the cell coat are less labeled and more conservative. The bulk of newly synthesized GAG/PG is secreted. This secretion appears an important property of macrophages the cause of which is speculative.