Disparate cytokine regulation of icam-1 in rat alveolar epithelial
cells and pulmonary endothelial cells in vitro.
Barton, William W., Steven Wilcoxen, Paul J. Christensen, and Robert
Paine.
Division of Pulmonary and Critical Care Medicine, Department of
Internal Medicine, University of Michigan, Ann Arbor, MI 48109
APStracts 2:0039L, 1995.
Intercellular adhesion molecule-1 (ICAM-1) is expressed at high levels
on type I alveolar epithelial cells in the normal lung and is induced
in vitro as type II cells spread in primary culture. In contrast, in
most non-hematopoetic cells ICAM-1 expression is induced in response
to inflammatory cytokines. We have formed the hypothesis that the
signals that control ICAM-1 expression in alveolar epithelial cells
are fundamentally different from those controlling expression in most
other cells. To test this hypothesis we have investigated the
influence of inflammatory cytokines on ICAM-1 expression in isolated
type II cells that have spread in culture and compared this response
to that of rat pulmonary artery endothelial cells (RPAEC). ICAM-1
protein, determined both by a cell-based ELISA and by Western blot
analysis, and mRNA were minimally expressed in unstimulated RPAEC,
but were significantly induced in a time and dose-dependent manner by
treatment with TNF-a, IL-1[beta], or IFN-g. In contrast, these
cytokines did not influence the constitutive high level ICAM-1
protein expression in alveolar epithelial cells and only minimally
effected steady-state mRNA levels. ICAM-1 mRNA half-life, measured in
the presence of actinomycin D, was relatively long at 7 hours in
alveolar epithelial cells and 4 hours in RPAEC. The striking lack of
response of ICAM-1 expression by alveolar epithelial cells to
inflammatory cytokines is in contrast to virtually all other
epithelial cells studied to date and supports the hypothesis that
ICAM-1 expression by these cells is a function of cellular
differentiation. Furthermore, we speculate that ICAM-1 may serve
different functions along the alveolar epithelial cell surface than
those traditionally attributed to ICAM-1 expressed on endothelial
cells within the vascular space.
Received 6 December 1994; accepted in final form 7 March 1995.
APS Manuscript Number L347-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 March 1995.