Biosynthesis of Chondroitin Sulfate Proteoglycan by P388D! Macrophage-like Cell Line

Macrophages are In large part responsible for the subendothellal deposition of llpld within the artery wall during the early stages of atherogenesls. Proteoglycans secreted by these cells may play a role In this pathological process either by trapping llpoprotelns In the extracellular matrix or by enhancing the formation of llpld-laden foam cells. The synthesis and secretion of proteoglycan was studied In the P388D, macrophage-llke cell line cultured In the presence of "S-sulfate. The radlolabeled proteoglycan had a Kd of 0.69 on Sepharose CL-2B corresponding to an Mr of 2.8x10*. It consisted of approximately 13 chondroitin sulfate chains of U, 20 000 attached to a core protein with an M, of 18 000. The chondroitin sulfate chains contained both M-acetylgalactosamlne 6-sulfate and N-acetylgalactosamlne 4sulfate residues. No dlsulfated N-acetylgalactosamlne residues were present The P388D, proteoglycan bound specifically to Immobilized human low density llpoproteln. These results suggest that, In the focal regions of the arterial wall In which macrophages are found during the development of fatty streaks, proteoglycans secreted by these cells may affect the transport and cellular metabolism of plasmaderived llplds. (Arteriosclerosis 8:535-543, September/October 1988)