ROS (reactive oxygen species) generated by hypoxia facilitate the vascular inflammatory response, but whether systemic hypoxia influences leucocyte bactericidal activity by modulating circulatory redox status remains unclear. The present study elucidates how various hypoxic interventions influence the bactericidal activity of PMNs (polymorphonuclear leucocytes) following treatment with an antioxidant, vitamin E (D-α-tocopheryl acetate). Forty healthy sedentary men were randomly assigned to vitamin E (n=20) and placebo (n=20) groups. At 1 h following oral administration of 1000 i.u. of vitamin E or placebo, each subject in the two groups was randomly exposed to 12%, 15%, 18% and 21% O2 for 2 h in a normobaric hypoxia chamber. The results demonstrated that exposure to 12% O2 in the placebo group increased urinary 8-isoprostane and plasma malondialdehyde levels and decreased plasma total antioxidant content and superoxide dismutase activity, but did not alter plasma complement-C3a desArg/C4a desArg/C5a concentrations. Moreover, this hypoxic exposure also increased the chemotaxis of PMNs by exposure to N-formyl-Met-Leu-Phe, the phagocytosis of PMNs to Escherichia coli and the release of PMN oxidant products by E. coli, processes which were accompanied by increased expressions of L-selectin, LFA-1 (lymphocyte function-associated antigen 1), Mac-1, FcγIIIBR, C1qRp and C5aR on PMNs. However, exposure to 12% O2 in the vitamin E group did not influence expression of the opsonic/complement receptors on PMNs, and the chemotactic, phagocytic or oxidative burst activities of PMN, whereas the circulatory redox status and complement fragment levels were unaltered following this hypoxic exposure and pretreatment with vitamin E. Additionally, the circulatory redox status, complement systems, PMN-mediated bactericidal processes and the opsonic/complement receptors on PMNs were constant following exposure to 15%, 18% or 21% O2 in the two groups. We conclude that exposure to 12% O2 promotes the chemotactic, phagocytic and oxidative burst activities of PMNs, possibly by increasing lipid peroxidation and decreasing antioxidative capacity. However, this hypoxic effect on PMN bactericidal activity is ameliorated by pretreatment with vitamin E.
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Research Article| May 01 2009
Systemic hypoxia enhances bactericidal activities of human polymorphonuclear leuocytes
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Jong-Shyan Wang, Huang-Chun Liu; Systemic hypoxia enhances bactericidal activities of human polymorphonuclear leuocytes. Clin Sci (Lond) 1 June 2009; 116 (11): 805–817. doi: https://doi.org/10.1042/CS20080224
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