COEXPRESSION OF HEAT-SHOCK-PROTEIN-60 AND INTERCELLULAR-ADHESION MOLECULE-1 IS RELATED TO INCREASED ADHESION OF MONOCYTES AND T-CELLS TO AORTIC ENDOTHELIUM OF RATS IN RESPONSE TO ENDOTOXIN

Bacterial cell-wall lipopolysaccharide (LPS) is the main endotoxin con tributing to local inflammation and systemic toxicity during Gram-nega tive infections and induces aortic endothelial injury with or without cell death and replication followed by increased leukocyte adhesion. H eat-shock protein (hsp) 60 is under study in our laboratory as a poten tial antigen inducing immunologic attack to endothelial cells in ather ogenesis. To investigate the mechanism of LPS-induced endothelial inju ry and the phenotypes of adhering cells, Lewis rats were treated in vi vo or, in aortic organ cultures, with LPS to determine the expression of intercellular-adhesion molecule-1 (ICAM-1) and hsp60 on aortic endo thelium and to characterize phenotypes of adhering leukocytes. Increas ed ICAM-1 expression by aortic endothelium was observed as early as 3 hr after LPS injection and persisted up to 72 hr, whereas elevated lev els of hsp60 were found between 6 and 48 hr. In vitro application of v arious types of stress, such as LPS, H2O2, and high temperature, not o nly stimulated endothelial expression of hsp60 but, concomitantly, tha t of ICAM-1. The number of adhering leukocytes was significantly incre ased on aortic endothelium 6 hr after LPS administration, and the pred ominant leukocytes adhering to stressed endothelium were monocytes (80 %) and T lymphocytes (8 to 20%). In organ cultures of rat aortic intim a, LPS, and H2O2 evoked increased leukocyte adhesion, which proved to be selective, because adherent leukocytes were mostly la(+) monocytes and T cells, i.e., activated. Adhering T cells were gamma/delta antige n-receptor positive in 8 to 16% after LPS stress, whereas these cells amount to only 2 to 4% of peripheral blood T cells. Blocking of adhesi on molecules ICAM-1, LFA-1 alpha, and/or LFA-1 beta reduced adhesion u p to 34%. Increased coordinated LPS-dependent expression of hsp60 and ICAM-1 correlates with monocyte and T-cell adhesion to aortic endothel ium. These observations may be significant for elucidating the mechani sm of the initiating events in the development of atherosclerosis.