Chen Q, Banick P D, Thom S R
University of Pennsylvania, Institute for Environmental Medicine, Philadelphia, USA.
J Pharmacol Exp Ther. 1996 Mar;276(3):929-33.
We hypothesized that hyperbaric oxygen caused a metabolic derangement in polymorphonuclear leukocytes that impaired the function of B2 integrins. Isolated neutrophils from rats that had been exposed to 3 atm oxygen for 45 min failed to exhibit B2 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 oxygen was found to inhibit cGMP synthesis that normally occurred when cells were stimulated by passage through nylon columns, and exposure to PMA or dithioerythritol reestablished cGMP synthesis. Cells adherent to plastic plates synthesized cGMP when they were exposed to N-formyl-methionyl-leucine-phenylalanine (FMLP) or PMA. Neutrophils from rats exposed to hyperbaric oxygen synthesized cGMP in response to PMA but failed to respond to FMLP, although hyperbaric oxygen did not alter the affinity of the FMLP receptor or its associated G protein. Dithioerythritol restored the cGMP synthetic ability of adherent neutrophils in response to FMLP. We conclude that hyperbaric oxygen inhibits B2 integrin-dependent adherence because it impairs cGMP synthesis by activated neutrophils.
我们推测，高压氧会导致多形核白细胞发生代谢紊乱，从而损害β2整合素的功能。从暴露于3个大气压氧气45分钟的大鼠中分离出的中性粒细胞，无法表现出β2整合素依赖性地黏附于尼龙柱或纤维蛋白原包被的平板上。在用8-溴-cGMP、佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）或还原剂二硫苏糖醇孵育细胞后，黏附得以恢复。研究发现，高压氧会抑制细胞通过尼龙柱刺激时正常发生的cGMP合成，而暴露于PMA或二硫苏糖醇可恢复cGMP合成。黏附于塑料平板上的细胞在暴露于N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）或PMA时会合成cGMP。暴露于高压氧的大鼠的中性粒细胞对PMA有反应而合成cGMP，但对FMLP无反应，尽管高压氧并未改变FMLP受体或其相关G蛋白的亲和力。二硫苏糖醇恢复了黏附的中性粒细胞对FMLP的cGMP合成能力。我们得出结论，高压氧抑制β2整合素依赖性黏附是因为它损害了活化中性粒细胞的cGMP合成。
