Enhanced leucocyte adhesion to interleukin-1 beta stimulated vascular smooth muscle cells is mainly through intercellular adhesion molecule-1.
OBJECTIVE
The aim was to investigate whether interleukin-1 beta (IL-1 beta) plays a role in modulating the adhesion of monocytes and neutrophils to vascular smooth muscle cells, and to identify what molecules on these cells may be involved in the adhesion.


METHODS
Rat aortic smooth muscle cells were challenged with IL-1 beta and tested for adhesion of prelabelled monocytes and neutrophils. Northern analysis, reverse transcription/polymerase chain reaction (RT/PCR), and immunocytochemical staining were used to measure the changes of intercellular adhesion molecule-1 (ICAM-1) and other adhesion molecules in response to IL-1 beta stimulation. Neutralising antibody against ICAM-1 was used to demonstrate a role of ICAM-1 in this IL-1 beta induced adhesion.


RESULTS
IL-1 beta induced the adhesion of monocytes and neutrophils to aortic smooth muscle cells in a concentration and time dependent manner. IL-1 beta-induced adhesion was inhibited by preincubation of the cells with an IL-1 receptor antagonist (IL-1ra). Northern analysis and RT/PCR showed that ICAM-1 mRNA represents a predominant adhesion molecule induced by IL-1 beta, and that the expression of ICAM-1 mRNA precedes and parallels the induced adhesion profiles of aortic smooth muscle cells for leucocytes. Immunocytochemical staining confirmed the IL-1 beta induced ICAM-1 expression on the smooth muscle cells. Moreover, a monoclonal anti-rat ICAM-1 antibody produced a concentration dependent inhibition of the IL-1 beta induced adhesion of monocytes and neutrophils to the smooth muscle cells.


CONCLUSIONS
IL-1 beta actively regulates functional ICAM-1 expression in vascular smooth muscle cells. The IL-1 beta-induced expression of ICAM-1 on the smooth muscle cells may be an important contributor to the increased adhesion by monocytes and neutrophils to these cells and suggests that IL-1 beta might play a role in the proinflammatory and immune functions of the modified smooth muscle cells during atherosclerosis and restenosis.
Wang
X
X
Department of Cardiovascular Pharmacology, Smithkline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Feuerstein
G Z
GZ
Clark
R K
RK
Yue
T L
TL
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology; D001483:Base Sequence; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D016133:Polymerase Chain Reaction; D051381:Rats
D017931:DNA Primers; D007375:Interleukin-1; D018799:Intercellular Adhesion Molecule-1