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.
Woenckhaus
C
C
Institute of Pathology, Philipps University of Marburg, Germany.
Kaufmann
A
A
Bussfeld
D
D
Gemsa
D
D
Sprenger
H
H
Gröne
H J
HJ
D001161:Arteriosclerosis / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D006997:Hypochlorous Acid