Hypochlorite-modified LDL: chemotactic potential and chemokine induction in human monocytes

Within blood vessels the accumulation of monocytes/macrophages at sites of modified lipoproteins is an important feature in atherosclerosis. Recently the presence of LDL and other proteins modified by hypochlorous acid (HOCl-LDL) was demonstrated in human atherosclerotic vessels and human inflammatory kidney disease by immunohistology and protein chemistry. Chemokines contribute to a specific and directed migration of inflammatory cells. IL-8 (alpha-chemokine) attracts mainly neutrophils and distinct T-cell subsets while MCP-1 (beta-chemokine) preferentially acts on monocytes/macrophages. In the present study it was postulated that HOCl-LDL may induce and amplify inflammatory reactions by the induction of chemokine synthesis in local monocytes. After exposure of human monocytes to HOCl-LDL, it was found that mRNA and protein of the 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 detectable. We propose that HOCl-LDL may represent a form of LDL modification in the atherosclerotic process which initiates leukocyte infiltration; these mononuclear cells have been observed in the early stages of atherosclerosis.