HYPOCHLORITE-MODIFIED LDL - CHEMOTACTIC POTENTIAL AND CHEMOKINE INDUCTION IN HUMAN MONOCYTES

Within blood vessels the accumulation of monocytes/macrophages at site s of modified lipoproteins is an important feature in atherosclerosis. Recently the presence of LDL and other proteins modified by hypochlor ous acid (HOCl-LDL) was demonstrated in human atherosclerotic vessels and human inflammatory kidney disease by immunhistology and protein ch emistry. Chemokines contribute to a specific and directed migration of inflammatory cells. IL-8 (alpha-chemokine) attracts mainly neutrophil s and distinct T-cell subsets while MCP-1 (beta-chemokine) preferentia lly acts on monocytes/macrophages. In the present study it was postula ted that HOCl-LDL may induce and amplify inflammatory reactions by the induction of chemokine synthesis in local monocytes. After exposure o f human monocytes to HOCl-LDL, it was found that mRNA and protein of t he chemokine IL-8 was strongly induced, while the chemokine MCP-1 was not. HOCl-LDL itself led to a chemotactic migration of neutrophils. A chemotactic response of human monocytes toward HOCl-LDL was not detect able. We propose that HOCl-LDL may represent a form of LDL modificatio n in the atherosclerotic process which initiates leukocyte infiltratio n; these mononuclear cells have been observed in the early stages of a therosclerosis. (C) 1998 Academic Press.