ROLE OF THE GRO FAMILY OF CHEMOKINES IN MONOCYTE ADHESION TO MM-LDL-STIMULATED ENDOTHELIUM

We have previously shown that treatment of endothelial cells with mini mally modified LDL (MM-LDL) induces the binding of monocytes to unknow n endothelial receptor molecules. We now report that a member of the G RO family of chemokines plays a role in MM-LDL-induced monocyte bindin g. A cDNA library made from rabbit aortic endothelial cells (RAEC) tre ated with MM-LDL was expression screened for molecules inducing bindin g of a human monocyte cell line (THP-1). A cDNA was isolated with 75% homology to GRO. GRO mRNA levels were significantly elevated after exp osure of RAEC or human aortic endothelial cells (HAEC) to MM-LDL. HAEC treated with RIM-LDL displayed an increase in a surface-associated pr otein that bound to antibody against GRO despite low levels of GRO in the medium. Antibody to GRO significantly inhibited the binding of mon ocytes to MM-LDL-treated RAEC and HAEC. The increase in GRO expression and monocyte binding were reduced by incubating MM-LDL-treated endoth elial cells with heparin (in a method that releases heparan sulfate bo und molecules from the cell surface). These results suggest that GRO r elated chemokines are bound to the surface of MM-LDL-treated endotheli al cells and may contribute to the monocyte adhesion induced by MM-LDL .