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

Clin Immunol Immunopathol. 1998 Jan;86(1):27-33. doi: 10.1006/clin.1997.4453.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteriosclerosis / physiopathology
  • Chemokine CCL2 / biosynthesis
  • Chemotactic Factors / pharmacology*
  • Chemotaxis, Leukocyte / drug effects*
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypochlorous Acid / pharmacology
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Lipoproteins, LDL / pharmacology*
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Neutrophils / drug effects*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Chemokine CCL2
  • Chemotactic Factors
  • Interleukin-8
  • Lipoproteins, LDL
  • RNA, Messenger
  • Hypochlorous Acid