Lipoprotein lipase enhances human monocyte adhesion to aortic endothelial cells.
Lipoprotein lipase (LPL)-mediated lipolysis of very low density lipoprotein (VLDL) has been demonstrated to increase U937 monocyte adhesion to endothelial cells. In the present study, we evaluated the ability of LPL to enhance human monocyte adhesion to bovine aortic endothelial cells (BAEC) in the absence of exogenous lipoproteins. Exposure of BAEC to 1 microgram/ml LPL at 37 degrees C resulted in a significant increase in monocyte adhesion over control values. Addition of VLDL in the culture media further enhanced the LPL effect. A significant increase in monocyte adhesion was also observed when BAEC were incubated with LPL at 4 degrees C. Heparin or heparinase treatment of BAEC totally abolished the LPL stimulatory effect on monocyte adhesion. In addition, incubation of monocytes with heparinase suppressed the ability of LPL to stimulate monocyte adhesion to endothelial cells. These treatments also markedly decreased LPL binding to the monocyte and endothelial cell surfaces. In contrast to native LPL, heat inactivated or phenylmethylsulfonyl fluoride (PMSF)-treated LPL did not increase monocyte adhesion to BAEC. Finally, incubation of LPL in the presence of the 5D2 antibody resulted in a total suppression of the LPL-induced monocyte adhesion to BAEC. Taken together, these data demonstrate that LPL activity plays an important role in LPL-induced monocyte adhesion and that LPL binding to heparan sulfate proteoglycans expressed on both monocytes and endothelial cells surfaces is required for the enhanced monocyte adhesion. These results suggest a new mechanism by which LPL may promote the development of atherosclerosis, that of facilitating monocyte adhesion to the endothelium.
Mamputu
J C
JC
Louis-Charles Simard Research Center, Notre-Dame Hospital, Department of Nutrition, University of Montreal, Quebec, Canada.
Desfaits
A C
AC
Renier
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D019763:Heparin Lyase / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011489:Protein Denaturation
D000911:Antibodies, Monoclonal; D006493:Heparin; D008071:Lipoprotein Lipase; D019763:Heparin Lyase