Expression of the Macrophage Scavenger Receptor in Atheroma

Abstract

Scavenger receptors mediate internalization of modified lipoproteins and foam cell transformation of monocyte-derived macrophages. Their expression is independent of the intracellular cholesterol content but is modulated by immune-derived cytokines. We investigated macrophage scavenger receptor (MSR) expression in monocyte-macrophages from human peripheral blood and in atherosclerotic lesions and analyzed its relationship to T lymphocytes and immunoregulatory cytokines by immunohistochemistry and polymerase chain reaction (PCR). Antibodies specific for the 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. CD3-positive T cells and α-actin–positive smooth muscle cells exhibited no reactivity to the anti-MSR antibodies. The frequency of cells stained with antibodies to MSR type I was equal to that of cells stained for type II, suggesting that most macrophages coexpress both isoforms. Reverse transcription (RT)–PCR analysis confirmed that both MSR isoforms were expressed in all plaques examined. There was, however, a tendency toward a lower immunohistochemical staining intensity for MSR type I and a decreased number of lipid-rich foam cells in T cell–rich areas. The mRNAs for interleukin-2 and interferon-γ, 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-γ downregulates MSR expression, these observations suggest a potential mechanism for local regulation of MSR expression in the atherosclerotic plaque.