EXPRESSION OF THE MACROPHAGE SCAVENGER RECEPTOR IN ATHEROMA - RELATIONSHIP TO IMMUNE ACTIVATION AND THE T-CELL CYTOKINE INTERFERON-GAMMA

Citation
Yj. Geng et al., EXPRESSION OF THE MACROPHAGE SCAVENGER RECEPTOR IN ATHEROMA - RELATIONSHIP TO IMMUNE ACTIVATION AND THE T-CELL CYTOKINE INTERFERON-GAMMA, Arteriosclerosis, thrombosis, and vascular biology, 15(11), 1995, pp. 1995-2002
Citations number
39
Categorie Soggetti
Cardiac & Cardiovascular System","Peripheal Vascular Diseas
ISSN journal
10795642
Volume
15
Issue
11
Year of publication
1995
Pages
1995 - 2002
Database
ISI
SICI code
1079-5642(1995)15:11<1995:EOTMSR>2.0.ZU;2-2
Abstract
Scavenger receptors mediate internalization of modified lipoproteins a nd foam cell transformation of monocyte-derived macrophages. Their exp ression is independent of the intracellular cholesterol content but is modulated by immune-derived cytokines. We investigated macrophage sca venger receptor (MSR) expression in monocyte-macrophages from human pe ripheral blood and in atherosclerotic lesions and analyzed its relatio nship to T lymphocytes and immunoregulatory cytokines by immunohistoch emistry and polymerase chain reaction (PCR). Antibodies specific for t he two MSR. isoforms were generated by immunizing rabbits with isoform -specific synthetic peptides conjugated to keyhole limpet hemocyanin. In human atherosclerotic plaques, these antibodies stained macrophages and foam cells in a pattern that corresponded to the distribution of the macrophage marker CD68. CDS-positive T cells and alpha-actin-posit ive smooth muscle cells exhibited no reactivity to the anti-MSR antibo dies. The frequency of cells stained with antibodies to MSR type I was equal to that of cells stained for type II, suggesting that most macr ophages coexpress both isoforms. Reverse transcription (RT)-PCR analys is confirmed that both MSR isoforms were expressed in all plaques exam ined. There was, however, a tendency toward a lower immunohistochemica l staining intensity for MSR type I and a decreased number of lipid-ri ch foam cells in T cell-rich areas. The mRNAs for interleukin-2 and in terferon-gamma, two major products of activated T cells, were detected by RT-PCR in all plaques tested. This indicates that activation of T lymphocytes occurs in atherosclerotic plaques. Since interferon-gamma downregulates MSR expression, these observations suggest a potential m echanism for local regulation of MSR expression in the atherosclerotic plaque.