Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1995-2002
© 1995 American Heart Association, Inc.
Articles |
Expression of the Macrophage Scavenger Receptor in Atheroma
Relationship to Immune Activation and the T-Cell Cytokine Interferon-
From the Departments of Laboratory Medicine (Y-j.G., S.N., M.B.) and Surgery (J.H.), Gothenburg University, Gothenburg, Sweden, and King Gustaf V Research Institute (M.B., S.S., G.K.H.), Karolinska Institute, Stockholm, Sweden.
Correspondence to Prof Göran K. Hansson, King Gustaf V Research Institute, Karolinska Hospital, S-17176 Stockholm, Sweden.
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 
-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-
, 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- downregulates MSR
expression, these observations suggest a potential mechanism for local
regulation of MSR expression in the atherosclerotic plaque.
Key Words: atherosclerosis • scavenger receptor • LDL • LDL oxidation • macrophages • T lymphocytes • immunohistochemistry • PCR
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