From the 1. Medizinische Klinik und Deutsches Herzzentrum, Technische
Universität München, Germany.
Correspondence to Prof Dr Franz-Josef Neumann, 1. Medizinische Klinik und Deutsches Herzzentrum, Technische Universität München, Lazarettstr 36, D-80636 München, Germany.
Background—Plaque erosion is a
frequent finding in sudden death due to coronary thrombosis.
The present study sought to investigate whether monocyte adhesion
to human aortic vascular smooth muscle cells (VSMCs) induces
procoagulant activity (PCA) and whether this could be mediated by
intercellular adhesion molecule-1 (ICAM-1).
Methods and Results—We incubated mononuclear cells (MNCs) with
VSMCs and ICAM-1–transfected Chinese hamster ovary (CHO) cells,
investigated monocyte tissue factor (TF) mRNA expression by Northern
blot analysis and TF protein expression by ELISA, and measured
PCA. Incubation of MNCs with VSMCs for 6 hours increased PCA from
0.7±0.1 to 166.0±37.9 mU/105 cells
(P=0.007), which could be inhibited in a dose-dependent
manner by the addition of blocking anti–ICAM-1 monoclonal antibodies.
Prestimulation of VSMCs with interleukin-1ß enhanced surface ICAM-1
expression significantly but did not induce PCA in VSMCs. Incubation of
MNCs with prestimulated VSMCs led to a further increase in PCA to
239.9±27.9 mU/105 cells (P=0.02 compared
with incubation with unstimulated VSMCs). Incubation of MNCs with VSMCs
enhanced TF mRNA after 2 hours and significantly increased TF protein
content after 6 hours. Incubation of purified monocytes with
ICAM-1–transfected CHO cells increased PCA from 1.2±0.2 to 81.9±3.3
mU/105 cells (P<0.001 compared with
incubation with untransfected CHO cells) after 6 hours. This effect
could be inhibited significantly by the addition of blocking anti-CD18,
anti-CD11b, or anti-CD11c monoclonal antibodies. Similar results were
obtained for MNCs.
Conclusions—Monocyte adhesion to VSMCs induces TF mRNA and
protein expression and monocyte PCA, which is regulated by
ß2-integrin–mediated monocyte adhesion to ICAM-1 on
VSMCs.
© 1998 American Heart Association, Inc.
Basic Science Reports
Enhancement of Monocyte Procoagulant Activity by Adhesion on Vascular Smooth Muscle Cells and Intercellular Adhesion Molecule-1–Transfected Chinese Hamster Ovary Cells
Key Words: muscle, smooth • cells • cell adhesion molecules • coagulation • tissue
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