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(Received for publication, February 25, 1997, and in revised form, August 11, 1997)
From the a Cardiovascular Institute and i Division of
Thrombosis Research, b Department of Medicine, the
k Department of Biochemistry, and the h Department of
Pathology, The Mount Sinai School of Medicine,
New York, New York 10029, the d Department of Medicine, the
e Dana Farber Cancer Institute, Harvard Medical School,
Boston, Massachusetts 02115, the f Gladstone Institute of
Cardiovascular Disease, San Francisco, California 94141, and the
g Cardiovascular Research Institute, Department of Medicine,
University of California, San Francisco, California 94143
Monocyte chemoattractant protein-1 (MCP-1) is a
C-C chemokine thought to play a major role in recruiting monocytes to
the atherosclerotic plaque. Tissue factor (TF), the initiator of
coagulation, is found in the atherosclerotic plaque, macrophages, and
human aortic smooth muscle cells (SMC). The exposure of TF during
plaque rupture likely induces acute thrombosis, leading to myocardial infarction and stroke. This report demonstrates that MCP-1 induces the
accumulation of TF mRNA and protein in SMC and in THP-1
myelomonocytic leukemia cells. MCP-1 also induces TF activity on the
surface of human SMC. The induction of TF by MCP-1 in SMC is inhibited by pertussis toxin, suggesting that the SMC MCP-1 receptor is coupled
to a Gi-protein. Chelation of intracellular calcium
and inhibition of protein kinase C block the induction of TF by MCP-1, suggesting that in SMC it is mediated by activation of phospholipase C. SMC bind MCP-1 with a Kd similar to that previously reported for macrophages. However, mRNA encoding the macrophage MCP-1 receptors, CCR2A and B, is not present in SMC, indicating that
they possess a distinct MCP-1 receptor. These data suggest that in
addition to being a chemoattractant, MCP-1 may have a procoagulant function and raise the possibility of an autocrine pathway in which MCP-1, secreted by SMC and macrophages, induces TF activity in these same cells.
Volume 272, Number 45,
Issue of November 7, 1997
pp. 28568-28573
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Tissue Factor Is Induced by Monocyte Chemoattractant Protein-1 in
Human Aortic Smooth Muscle and THP-1 Cells
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