Inhibition of human neutrophil b2 integrin-dependent adherence by
hyperbaric oxygen.
Thom, Stephen R., Ignacio Mendiguren, Kevin Hardy, Todd Bolotin,
Donald Fisher, Monique Nebolon, and Laurie Kilpatrick.
University of Pennsylvania, Institute for Environmental Medicine,
Department of Emergency Medicine, Division of Pulmonary and Critical
Care Medicine, and Childrens' Hospital of Philadelphia Department of
Immunology
APStracts 3:0247C, 1996.
Animal and clinical investigations have reported that exposure to
hyperbaric oxygen improved the outcome of some reperfusion injuries.
Animal studies have suggested that this may be due to an inhibition
of leukocyte adherence to injured endothelium. This investigation
tested the hypothesis that exposure to hyperbaric oxygen would
inhibit [beta]2 integrin dependent adherence of human neutrophils.
Subjects were exposed to oxygen at partial pressures of up to 3
atmospheres absolute for 45 minutes and neutrophil binding to nylon
columns and to fibrinogen-coated surfaces was measured. Exposure to
oxygen at 2.8 or 3.0 atmospheres absolute inhibited [beta]2 integrin
dependent neutrophil adherence, but had no effect on the cell-surface
expression of [beta]2 integrins, respiratory burst in response to
phorbol ester, or non-[beta]2 integrin dependent adherence to plastic
plates coated with a fibronectin-like protein. [beta]2 integrin
adherence was restored by incubating blood with 8 bromo-cyclic GMP
and hyperbaric oxygen inhibited synthesis of cyclic GMP by
neutrophils stimulated with formyl-methionyl leucine phenylalanine.
In studies with cell fractions, the activity of membrane guanylate
cyclase was found to be increased by incubation with formyl-methionyl
leucine phenylalanine, as well as by atrial natriuretic peptide plus
ATP. Hyperbaric oxygen had no effect on the basal activity of soluble
or membrane-bound guanylate cyclase. However, hyperbaric oxygen
inhibited the function of both the extracellular binding domain of
membrane guanylate cyclase, as well as intracellular catalytic
activity. There are approximately 7300 membrane guanylate cyclase
molecules/ cell, based on binding studies with atrial natriuretic
peptide, with a Kd of approximately 450 pM. Hyperbaric oxygen
inhibits the function of human neutrophil [beta]2 integrins by a
process linked to impaired synthesis of cyclic GMP.
Received 12 April 1996; accepted in final form 23 February 1996.
APS Manuscript Number C204-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996