DOWN-REGULATION OF CD11B AND CD18 EXPRESSION IN ATHEROSCLEROTIC LESION-DERIVED MACROPHAGES

Monocyte/macrophages play an important role in the development of athe rosclerosis. Electron microscopic evidence suggests that in the early stages, lipid laden monocytes leave the lesion to reenter the circulat ion. This reverse monocyte traffic ceases as the lesion develops. We h ypothesize that monocyte/macrophages may not be able to exit the lesio n and reenter the circulation because of the reduced expression of CD1 1/CD18 integrins. We have compared CD11b and CD18 expression of periph eral blood monocytes from normal rabbits (NMo) to atherosclerotic lesi on-derived macrophages (AthMo) by anti-CD11b and anti-CD 18 antibody s taining, followed by flow cytometry and immunohistochemical staining. AthMo were isolated from aortic lesions of rabbits fed 2 per cent chol esterol diet following balloon angioplasty. AthMo were separated into two regions based on their size and granularity by flow cytometry. All macrophages stained positively with RAM 11. Our results indicated tha t NMo showed a strong cell surface expression of CD11b and CD18. The l ess granular and smaller AthMo showed little anti-CD11b or anti-CD18 a ntibody staining, indicating very little CD11b or CD18 expression. The more granular and larger cells showed surface expression of both CD11 b and CD18. With respect to CD18, over 90 per cent of NMo expressed CD 18, only 37 per cent of the large granular AthMo, and less than 1 per cent of the smaller, less granular AthMo stained positive for CD18. Im munohistochemical studies revealed strong surface expression of CD11b and CD18 on normal monocytes. Expression of these surface markers on a therosclerotic lesion-derived macrophages is markedly reduced. These r esults suggest that there is a strong down regulation of CD11b and CD1 8 integrin expression in AthMo compared to NMo from which they are der ived.