© 1997 American Heart Association, Inc.
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Macrophages Isolated From Human Atherosclerotic Plaques Produce IL-8, and Oxysterols May Have a Regulatory Function for IL-8 Production
the Wallenberg Laboratory for Cardiovascular Research, Goteborg University, Sweden.
Correspondence to Dr O. Wiklund, Wallenberg Laboratory, Sahlgren's Hospital, S-413 45 Goteborg, Sweden. E-mail wiklund@wlab.wall.gu.se.
Oxysterols are biologically active molecules generated during oxidation of LDL. Several of these oxysterols were found in macrophage-derived foam cells from human atherosclerotic tissue (eg, 7-hydroxycholesterol, 7-ketocholesterol, 5-epoxycholesterol, and 25-hydroxycholesterol). A specific stimulation of interleukin-8 (IL-8) production by oxidized LDL (oxLDL) has been shown by other investigators. In foam cells from human atherosclerotic tissue, we found high levels of IL-8 (183.1 pg/106 cells) compared with monocytes (23.2 pg/106 cells) or monocyte-derived macrophages in culture (1.5 pg/106 cells). When monocytes and monocyte-derived macrophages, in vitro, were exposed to a series of different oxysterols, we found that all oxysterols tested had a tendency to stimulate IL-8 production but that 25-hydroxycholesterol was the most potent one. This stimulation of IL-8 production was time and dose dependent and could be blocked by cycloheximide. These results indicate that oxysterols in oxLDL may have a regulatory effect on IL-8 production. IL-8, a potent chemoattractant, may play a role in the recruitment of T lymphocytes and smooth muscle cells into the subendothelial space and may contribute to the formation of atherosclerotic lesions.
Key Words: atherosclerosis • foam cells • oxysterols • IL-8 • cell isolation
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