Original Contributions |
From the Pharmaceutical Frontier Research Laboratories, J.T. Central Pharmaceutical Research Institute, Yokohama, Japan.
Correspondence to Shosaku Narumi, MD, Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, 73-1, Hongo, Bunkyoku, Tokyo 113, Japan. E-mail snarumi{at}tka.att.ne.jp
AbstractWe examined the tissue
distribution of adhesion molecule gene expression in mice treated
intravenously with interleukin (IL)-1ß. E-selectin mRNA
expression was selectively induced in the heart by IL-1ß, but only
slight or no induction was observed in other organs. On the other hand,
intercellular adhesion molecule-1 mRNA expression was inducible in all
organs examined, although it showed the strongest induction in the lung
and the weakest responses in the brain and skin. Vascular cell adhesion
molecule-1 mRNA was also inducible in all organs with the exception of
the skin, but it was induced most markedly in the lung and the heart.
The accessibility of IL-1ß to the heart was less than that to other
organs except the brain. Similar tissue-specific induction of these
mRNAs was also seen when tumor necrosis factor (TNF)-
or
lipopolysaccharide was substituted for IL-1ß.
Analysis of E-selectin mRNA expression in the heart by in situ
hybridization indicated that expression was most prominent in
microvascular endothelial cells and some other stromal
cells, but this transcript was not seen in the lung. Although
intercellular adhesion molecule-1 mRNA expression was restricted to the
endothelium lining the capillaries and small arteries
in the heart, its distribution in the lung covered not only the
endothelium but also the cells composing the alveolar
septa. In contrast, vascular cell adhesion molecule-1 mRNA expression
was most prominent in endothelial cells of larger
vessels in both the heart and the lung. Our results demonstrate that
expression of adhesion molecules is tissue- and cell typespecific and
that endothelial cells differentially express adhesion
molecules depending on the size of the blood vessels.
Key Words: gene expression endothelium adhesion molecules interleukin-1ß tumor necrosis factor-
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