Cytokines regulate membrane-bound leukocyte elastase on
neutrophils: a novel mechanism for effector activity.
Owen, Caroline A., Melody A. Campbell, Steve S. Boukedes, Edward J.
Campbell.
Department of Medicine, University of Utah Health Sciences Center,
Salt Lake City, Utah, 84132; and Salt Lake VAMC, Salt Lake City,
Utah, 84148
APStracts 3:0187L, 1996.
Membrane-bound leukocyte elastase activity on neutrophils may have
potent pro-inflammatory effects. Herein, we report the effects of
tumor necrosis factor-[alpha] (TNF-[alpha]), platelet activating
factor (PAF), N-formyl-leucyl-methionyl-phenylalanine (fMLP), and
interleukin-8 (IL-8) on membrane-bound elastase expression. TNF
-[alpha] or PAF alone induced only 2-3 fold increases in membrane
-bound elastase, but exhibited marked dose- and time-dependent priming
effects for subsequent stimulation with fMLP or IL-8 (up to 20-fold
increases in membrane-bound HLE compared to unstimulated cells).
Optimally PAF-primed and fMLP-stimulated cells expressed 1.105 + SD
0.25 x 10-17 mol (6.65 + SD 1.51 x 106 molecules) of membrane-bound
elastase activity per cell, or 12% of the content of unstimulated
cells. Elastase binds to the cell surface by a charge-dependent
mechanism since: 1) incubation of cells with cationic molecules
abrogated agonist-induced upregulation of membrane-bound elastase;
and 2) elastase was progressively eluted from the cell surface by
solutions with increasing ionic strength. Thus, interactions between
pro-inflammatory mediators strikingly upregulate membrane-bound
elastase on neutrophils, which may promote inflammatory responses
and/or contribute to tissue injury.
Received 22 August 1996; accepted in final form 14 October 1996.
APS Manuscript Number L274-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996