Lysolecithin-induced alteration of subendothelial heparan sulfate proteoglycans increases monocyte binding to matrix.
The cause and consequence of altered proteoglycans in atherosclerosis are poorly understood. To determine whether proteoglycans affect monocyte binding, we studied the effects of heparin and proteoglycan degrading enzymes on THP-1 monocyte adhesion to subendothelial matrix (SEM). Monocyte binding increased about 2-fold after SEM was treated with heparinase. In addition, heparin decreased monocyte binding to fibronectin, a known SEM protein, by 60%. These data suggest that SEM heparan sulfate inhibits monocyte binding to SEM proteins. We next examined whether lysolecithin, a constituent of modified lipoproteins, affects endothelial heparan sulfate proteoglycan (HSPG) production and monocyte binding. Lysolecithin (10-200 microM) decreased total 35SO4 in SEM (20-75%). 2-fold more monocytes bound to SEM from lysolecithin treated cells than to control SEM. Heparinase treatment did not further increase monocyte binding to lysolecithin-treated SEM. HSPG degrading activity was found in medium from lysolecithin-treated but not control cells. 35SO4-labeled products obtained from labeled matrix treated with lysolecithin-conditioned medium were similar in size to those generated by heparinase. These data suggest that lysolecithin-treated endothelial cells secrete a heparanase-like activity. We hypothesize that decreased vessel wall HSPG, as occurs in atherogenic conditions, allows increased monocyte retention within the vessel and is due to the actions of an endothelial heparanase.
Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
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P
Sivaram
J C
JC
Obunike
I J
IJ
Goldberg
D000818:Animals; D001011:Aorta; D001345:Autoradiography / Q000379:methods; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002810:Chondroitinases and Chondroitin Lyases / Q000494:pharmacology; D017077:Culture Media, Conditioned; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans; D019763:Heparin Lyase; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011133:Polysaccharide-Lyases / Q000378:metabolism / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism
D002810:Chondroitinases and Chondroitin Lyases; D017077:Culture Media, Conditioned; D019812:Heparan Sulfate Proteoglycans; D019763:Heparin Lyase; D006497:Heparan Sulfate; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D011133:Polysaccharide-Lyases; D011509:Proteoglycans; D013431:Sulfates