Functional Inhibition of Leukocyte B₂ Integrins by Hyperbaric Oxygen in Carbon Monoxide-Mediated Brain Injury in Rats

Abstract

Exposure to hyperbaric oxygen [3 atmospheres absolute (ATA) for 45 min] inhibited carbon monoxide (CO)-mediated lipid peroxidation in the brains of rats by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion process known to be due to the action of leukocytes. The effect was the same whether treatment was given 24 hr before or up to 45 min after poisoning. Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, based on measurements of myeloperoxidase (MPO) in microvessel segments, but persistent adherence, which is due to B₂ integrins, did not occur. Exposing rats to 3 ATA pressure (0.21 ATA O₂) after CO poisoning had no significant effects. A progressive reduction in brain microvessel MPO titers occurred with exposure to O₂ at 1, 2, or 3 ATA after CO poisoning, but 1 ATA O₂ treatment did not significantly inhibit xanthine oxidase formation or lipid peroxidation. In vitro studies with polymorphonuclear leukocytes (PMN) from rats exposed to hyperbaric oxygen corroborated the absence of PMN B₂ integrin function, but when these cells were stimulated they exhibited normal B₂ integrin expression on their surface and also normal elastase release and superoxide radical production. Adherence functions of PMN that do not require B₂ integrins appeared to remain intact after exposure to hyperbaric oxygen, as peritoneal neutrophilia in response to a glycogen challenge was not inhibited. B₂ integrin function could be restored by incubating cells with 8 bromo cGMP, and incubation with phorbol ester stimulated the adherence function of both control and hyperbaric oxygen-exposed PMN. These results provide a clear mechanism for the inhibition of CO-mediated brain lipid peroxidation by hyperbaric oxygen and indicate that hyperoxia causes a discrete disturbance of PMN adherence function.