Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:1573-1579
© 1996 American Heart Association, Inc.
Articles |
Human Monocytes/Macrophages Release TNF-
in Response to Ox-LDL
the Department of Medicine, Karolinska Hospital, King Gustaf Vth Research Institute, Stockholm, Sweden.
Correspondence to Dr Stefan Jovinge, King Gustaf Vth Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail jovinge@instmed.ks.se.
The uptake of oxidatively modified low density lipoprotein (Ox-LDL) by intimal macrophages is believed to play a key role in the development of atherosclerosis. The present study demonstrates that Ox-LDL in low concentrations activates monocyte/macrophage release of factors that stimulate smooth muscle cell growth, whereas higher concentrations are inhibitory. Exposure of monocytes/macrophages to 8 µg/mL Ox-LDL increased expression of tumor necrosis factor-
(TNF-) mRNA but had no effect on interleukin-1ß, platelet-derived growth factor B and heparin-binding epidermal growth factor–like mitogen mRNA levels. Ox-LDL also stimulated monocyte/macrophage release of TNF- in a dose-dependent manner, with maximal effect at an LDL concentration of 8 µg/mL. Addition of TNF-–blocking antibodies to conditioned medium from monocytes/macrophages already exposed to Ox-LDL reduced mitogenic activity by 44.7±8.4% (P<.005). Stimulation of TNF- release by Ox-LDL was associated with activation of transcription factor AP-1, whereas the activity of transcription factor nuclear factor-
B remained unchanged. These findings suggest that enhanced secretion of TNF- by macrophages exposed to Ox-LDL may be involved in the formation of atherosclerotic lesions.
Key Words: atherosclerosis • oxidized LDL • smooth muscle cells • tumor necrosis factor- • AP-1
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