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
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.