Reconstituted high density lipoprotein modulates adherence of polymorphonuclear leukocytes to human endothelial cells.

A reconstituted high density lipoprotein (rHDL) containing human apolipoprotein A-I and phosphatidylcholine was tested for its ability to modify polymorphonuclear leukocyte (PMN) adherence to endothelial cells (EC) in vitro. EC stimulation for 4 h with lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF alpha) resulted in a four- to sixfold increase in PMN adherence. Concomitant stimulation of EC with LPS and rHDL virtually prevented the LPS-stimulated increase in PMN adherence. Changes in adherence were paralleled by alterations in adhesion molecule expression of EC. Concomitant EC stimulation with LPS and rHDL resulted in complete inhibition of the LPS-stimulated increase in expression of E-selectin and intercellular adhesion molecule 1 (ICAM-1). In contrast, rHDL reduced the TNF alpha-induced expression of adhesion molecules as well as the PMN adherence to TNF alpha-stimulated EC by approximately 10%. The CD11/CD18-mediated PMN adherence to EC as a consequence of PMN stimulation with calcium ionophore (A23187) was diminished in the presence of rHDL after 7 min incubation by 36.1 +/- 11.4% and after 15 min incubation by 45.1 +/- 7.4%. In addition, the A23187-stimulated increase in PMN adherence to fibrinogen-coated surfaces, mediated by CD11b/CD18, was virtually eliminated in the presence of rHDL and HDL, but not in the presence of apolipoprotein A-I or natural low density lipoprotein. FACS analysis showed that PMN treated with rHDL and subsequently washed were resistant to FMLP-induced CD11b/ CD18 up-regulation. In conclusion, these data indicate that rHDL decreases cell adhesion via two mechanisms: blocking LPS activity and modifying CD11b/CD18 up-regulation on PMN.