LIPOPROTEIN-LIPASE CAN FUNCTION AS A MONOCYTE ADHESION PROTEIN

Lipoprotein lipase (LPL) is made by several cell types, including macr ophages within the atherosclerotic lesion. LPL, a dimer of identical s ubunits, has high affinity for heparin and cell surface heparan sulfat e proteoglycans (HSPGs). Several studies have shown that cell surface HSPGs can mediate cell binding to adhesion proteins. Here, we tested w hether LPL, by virtue of its HSPG binding, could mediate monocyte adhe sion to surfaces. Monocyte binding to LPL-coated (1-25 mu g/mL) tissue culture plates was 1.4- to 7-fold higher than that of albumin-treated plastic. Up to 3-foId more monocytes bound to the subendothelial matr ix that had been pretreated with LPL. LPL also doubled the number of m onocytes that bound to endothelial cells (ECs). Heparinase and heparit inase treatment of monocytes or incubation of monocytes with heparin d ecreased monocyte binding to LPL. Heparinase/heparitinase treatment of the matrix also abolished the LPL-mediated increase in monocyte bindi ng. These results suggest that LPL dimers mediate monocyte binding by forming a ''bridge'' between matrix and monocyte surface HSPGs. Inhibi tion of LPL activity with tetrahydralipstatin, a lipase active-site in hibitor, did not affect the LPL-mediated monocyte binding. To assess w hether specific oligosaccharide sequences in HSPGs mediated monocyte b inding to LPL, competition experiments were performed by using known H SPG binding proteins. Neither antithrombin nor thrombin inhibited mono cyte binding to LPL. Next, we tested whether integrins were involved i n monocyte binding to LPL. Surprisingly, monocyte binding to LPL-coate d plastic and matrix was inhibited by approximate to 35% via Integrin- binding arginine-glycine-aspartic acid peptides. This result suggests that monocyte binding to LPL was mediated, in part, by monocyte cell s urface integrins. In summary, our data show that LPL, which is present on ECs and in the subendothelial matrix, can augment monocyte adheren ce. This increase in monocyte-matrix interaction could promote macroph age accumulation within arteries.