FUNCTIONAL INHIBITION OF RAT POLYMORPHONUCLEAR LEUKOCYTE B-2 INTEGRINS BY HYPERBARIC-OXYGEN IS ASSOCIATED WITH IMPAIRED CGMP SYNTHESIS

We hypothesized that hyperbaric oxygen caused a metabolic derangement in polymorphonuclear leukocytes that impaired the function of B-2 inte grins. Isolated neutrophils from rats that had been exposed to 3 atm o xygen for 45 min failed to exhibit B-2 integrin-dependent adherence to nylon columns or to fibrinogen-coated plates. Adherence was restored after cells were incubated with 8-bromo-cGMP, phorbol 12-myristate 13- acetate (PMA) or the reducing agent dithioerythritol. Hyperbaric oxyge n was found to inhibit cGMP synthesis that normally occurred when cell s were stimulated by passage through nylon columns, and exposure to PM A or dithioerythritol reestablished cGMP synthesis. Cells adherent to plastic plates synthesized cGMP when they were exposed to N-formyl-met hionyl-leucine-phenylalanine (FMLP) or PMA. Neutrophils from rats expo sed to hyperbaric oxygen synthesized cGMP in response to PMA but faile d to respond to FMLP, although hyperbaric oxygen did not alter the aff inity of the FMLP receptor or its associated G protein. Dithioerythrit ol restored the cGMP synthetic ability of adherent neutrophils in resp onse to FMLP. We conclude that hyperbaric oxygen inhibits B-2 integrin -dependent adherence because it impairs cGMP synthesis by activated ne utrophils.