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Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaques
1Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Abstract:
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.
Insights
Macrophages in carotid plaques significantly increase tumor necrosis factor (TNF) production compared to blood monocytes. This indicates a localized inflammatory response within these atheromatous plaques.
Area of Science:
- Cardiovascular Biology
- Immunology
- Atherosclerosis Research
Background:
- Macrophages are key immune cells implicated in the inflammatory processes of atherosclerosis.
- Cytokine production by macrophages within atherosclerotic plaques is crucial for disease progression.
Purpose of the Study:
- To investigate and compare the production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by macrophages from human carotid endarterectomy plaques versus non-carotid lesions.
- To determine the role of macrophages in the localized inflammatory response within atheromatous plaques.
Main Methods:
- Isolation of macrophages from human carotid endarterectomy and other atheromatous artery tissues.
- In vitro cell culture to assess cytokine release (TNF and IL-1).
- In situ immunohistology to evaluate cellular cytokine expression within plaque tissues.
Main Results:
- Macrophages from carotid plaques exhibited significantly augmented TNF release compared to blood monocytes and macrophages from non-carotid lesions.
- Cellular TNF expression was more prominent in macrophages within carotid plaques than in non-carotid lesions.
- Interleukin-1 (IL-1) production was not augmented in plaque macrophages, with only infrequent and low-intensity labeling observed.
Conclusions:
- Activated macrophages in carotid plaques show increased, localized production of TNF, but not IL-1.
- These findings highlight a selective augmentation of cytokine production within carotid plaques.
- Macrophages play an active role in the inflammatory response characteristic of atheromatous carotid plaques.