Increased cyclic amp levels in stimulated neutrophils inhibit their
adhesion to human bronchial epithelial cells.
Bloemen, Pauline G. M., Marja C. Van Den Tweel, Paul A. J. Henricks,
Ferdi Engels, Monique H. A. Kester, Peet G. F. Van De Loo, Frans J.
Blomjous, and Frans P. Nijkamp.
Department of Pharmacology and Pathophysiology, Utrecht Institute
for Pharmaceutical Sciences, Utrecht University, and Department of
Pathology, St. Antonius Hospital Nieuwegein, The Netherlands
APStracts 3:0204L, 1996.
Bronchial epithelial cells express the cell adhesion molecule ICAM-1
which mediates binding of activated neutrophils via interaction with
Mac-1 and/or LFA-1. In this study, we examined whether increased
intracellular levels of cyclic AMP affected neutrophil adhesion to
the human bronchial epithelial cells. It was found that the fMLP
-stimulated neutrophil adhesion was concentration-dependently
inhibited when the cyclic AMP analogues dibutyryl cyclic AMP or 8
-bromo-cyclic AMP were present. The [beta]-adrenergic receptor
agonists isoprenaline and salmeterol, in the presence of the
phosphodiesterase inhibitor 3-isobutyl-1-methylxantine (IBMX), were
also able to inhibit the fMLP-stimulated adhesion of neutrophils to
bronchial epithelial cells. These agonists in combination with IBMX
significantly increased the intracellular cyclic AMP level both in
neutrophils and epithelial cells. Preincubation of neutrophils with
the long-acting [beta]2-adrenergic receptor agonist salmeterol (in
the presence of IBMX) inhibited their fMLP-stimulated adhesion to
epithelial cells whereas pretreatment of epithelial cells did not
influence the adhesion process. When ethanol-fixed epithelium was
used, salmeterol pretreatment also diminished the adhesion of
stimulated neutrophils. Moreover, combinations of salmeterol or
isoprenaline with IBMX inhibited fMLP-upregulated Mac-1 expression.
Therefore, we conclude from these data that elevation of
intracellular cyclic AMP in the neutrophil inhibits stimulated
neutrophil adhesion to bronchial epithelial cells via Mac-1.
Received 26 March 1996; accepted in final form 1 November 1996.
APS Manuscript Number L97-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996