title: Inhibition of human neutrophil beta2-integrin-dependent adherence by hyperbaric O2.
abstract: Animal and clinical investigations have reported that exposure to hyperbaric O(2) 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 O(2) would inhibit beta2-integrin-dependent adherence of human neutrophils. Subjects were exposed to O(2) at partial pressures of up to 3 atmospheres absolute (ATA; 1 ATA = 0.1 MPa) for 45 min, and neutrophil binding to nylon columns and to fibrinogen-coated surfaces was measured. Exposure to O(2) at 2.8 or 3.0 ATA inhibited beta2-integrin-dependent neutrophil adherence but had no effect on the cell-surface expression of beta2-integrins, respiratory burst in response to phorbol ester, or non-beta2-integrin-dependent adherence to plastic plates coated with a fibronectin-like protein. beta2-Integrin adherence was restored by incubating blood with 8-bromoguanosine 3',5'-cyclic monophosphate (cGMP) and hyperbaric O(2) inhibited synthesis of cGMP by neutrophils stimulated with N-formyl-Met-Leu-Phe (FMLP). In studies of cell fractions, the activity of membrane guanylate cyclase was found to be increased by incubation with FMLP as well as by atrial natriuretic peptide (ANP) plus ATP. Hyperbaric O(2) had no effect on the basal activity of soluble or membrane-bound guanylate cyclase. However, hyperbaric O(2) inhibited the function of both the extracellular binding domain of membrane guanylate cyclase as well as intracellular catalytic activity. There are approximately 7,300 membrane guanylate cyclase molecules per cell, based on binding studies with ANP, with a dissociation constant of approximately 450 pM. Hyperbaric O(2) inhibits the function of human neutrophil beta2-integrins by a process linked to impaired synthesis of cGMP.
authors.affiliation: Department of Emergency Medicine, University of Pennsylvania, Philadelphia 19104-7037, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Thom
authors.forename: I
authors.initials: I
authors.lastname: Mendiguren
authors.forename: K
authors.initials: K
authors.lastname: Hardy
authors.forename: T
authors.initials: T
authors.lastname: Bolotin
authors.forename: D
authors.initials: D
authors.lastname: Fisher
authors.forename: M
authors.initials: M
authors.lastname: Nebolon
authors.forename: L
authors.initials: L
authors.lastname: Kilpatrick
mesh_terms: D000328:Adult; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D006931:Hyperbaric Oxygenation; D007158:Immunologic Techniques; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D016897:Respiratory Burst
chemical_list: D018821:CD18 Antigens; D009320:Atrial Natriuretic Factor; D005340:Fibrinogen; D006162:Guanylate Cyclase; D006152:Cyclic GMP