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Down regulation of CD11b and CD18 expression in atherosclerotic lesion-derived macrophages
1Department of Surgery, Loyola University Medical Center, Maywood, Illinois, USA.
Abstract:
Monocyte/macrophages play an important role in the development of atherosclerosis. Electron microscopic evidence suggests that in the early stages, lipid laden monocytes leave the lesion to reenter the circulation. This reverse monocyte traffic ceases as the lesion develops. We hypothesize that monocyte/macrophages may not be able to exit the lesion and reenter the circulation because of the reduced expression of CD11/CD18 integrins. We have compared CD11b and CD18 expression of peripheral blood monocytes from normal rabbits (NMø) to atherosclerotic lesion-derived macrophages (AthMø) by anti-CD11b and anti-CD 18 antibody staining, followed by flow cytometry and immunohistochemical staining. AthMø were isolated from aortic lesions of rabbits fed 2 per cent cholesterol diet following balloon angioplasty. AthMø were separated into two regions based on their size and granularity by flow cytometry. All macrophages stained positively with RAM 11. Our results indicated that NMø showed a strong cell surface expression of CD11b and CD18. The less granular and smaller AthMø showed little anti-CD11b or anti-CD18 antibody staining, indicating very little CD11b or CD18 antibody staining, indicating very little CD11b or CD18 expression. The more granular and larger cells showed surface expression of both CD11b and CD18. With respect to CD18, over 90 per cent of NMø expressed CD18, only 37 per cent of the large granular AthMø and less than 1 per cent of the smaller, less granular AthMø stained positive for CD18. Immunohistochemical studies revealed strong surface expression of CD11b and CD18 on normal monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Reduced CD11b/CD18 integrin expression on macrophages may prevent their exit from atherosclerotic lesions. This study investigated CD11b and CD18 levels in normal monocytes versus lesion-derived macrophages in rabbits, finding significantly lower expression in lesion macrophages.
Area of Science:
- Immunology
- Cardiovascular Research
- Cell Biology
Background:
- Monocyte/macrophages are crucial in atherosclerosis development.
- Reverse monocyte traffic from lesions to circulation ceases as lesions progress.
- Reduced CD11b/CD18 integrin expression is hypothesized to impede monocyte/macrophage exit from lesions.
Purpose of the Study:
- To compare CD11b and CD18 expression in normal rabbit monocytes (NMø) and atherosclerotic lesion-derived macrophages (AthMø).
- To investigate the role of CD11b/CD18 integrins in monocyte/macrophage egress from atherosclerotic plaques.
Main Methods:
- Isolated AthMø from aortic lesions of rabbits on a high-cholesterol diet post-angioplasty.
- Utilized anti-CD11b and anti-CD18 antibody staining.
- Employed flow cytometry and immunohistochemical staining for analysis.
- Separated AthMø based on size and granularity.
Main Results:
- Normal monocytes (NMø) exhibited strong surface expression of CD11b and CD18.
- Smaller, less granular AthMø showed minimal CD11b/CD18 expression (<1%).
- Larger, more granular AthMø had reduced CD18 expression (37%) compared to NMø (>90%).
Conclusions:
- Atherosclerotic lesion-derived macrophages display significantly reduced CD11b/CD18 integrin expression compared to normal monocytes.
- This downregulation of CD11b/CD18 may impair the ability of macrophages to exit atherosclerotic lesions.
- Findings suggest a mechanism contributing to the retention of macrophages within developing atherosclerotic plaques.