Expression of the macrophage scavenger receptor in atheroma. Relationship to immune activation and the T-cell cytokine interferon-gamma.
Scavenger receptors mediate internalization of modified lipoproteins and foam cell transformation of monocyte-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 alpha-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-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 mechanism for local regulation of MSR expression in the atherosclerotic plaque.
Geng
Y J
YJ
Department of Laboratory Medicine, Gothenburg University, Sweden.
Holm
J
J
Nygren
S
S
Bruzelius
M
M
Stemme
S
S
Hansson
G K
GK
D000368:Aged; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D007371:Interferon-gamma