Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaques.
The production of cytokines by atheromatous plaque macrophages from human endarterectomy tissue was assessed in vitro by short-term cell culture and in situ by immunohistology. Macrophages were isolated from plaques of 14 patients undergoing carotid endarterectomy and 7 patients undergoing reconstructive procedures on atheromatous distal aortic and femoral arteries. Tumor necrosis factor (TNF) and interleukin 1 (IL-1) production by plaque macrophages and blood monocytes isolated concurrently from these patients was assessed. TNF release by macrophages from carotid plaques (0.39 +/- 0.12 ng/10(6) cells/24 hours) was significantly augmented compared to the release by corresponding blood monocytes (0.014 +/- 0.011 ng/10(6) cells/24 hours, P = 0.03), and by macrophages from noncarotid lesions (0.038 +/- 0.036 ng/10(6) cells/24 hours, P < 0.04). Cellular TNF expression by macrophages within carotid plaques was also more prominent than in noncarotid lesions. By contrast, IL-1 production by plaque macrophages from both carotid and noncarotid plaques was not augmented compared to blood monocytes, and only infrequent and low-intensity labeling for IL-1 was present on macrophages within plaques from either group. These results provide functional and immunohistological evidence for increased production of TNF but not IL-1 by activated macrophages, indicating local and selective augmentation of cytokine production within carotid plaques. This suggests that macrophages play an active role in the inflammatory response within atheromatous carotid plaques.
Tipping
P G
PG
Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Hancock
W W
WW
D000368:Aged; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005263:Femoral Artery / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha