title: Studies on polymorphonuclear leukocyte bactericidal function: II. The role of oxidative stress.
abstract: We have previously detailed the effects of exogenous cytokines (IL-1 beta, TNF-alpha, and IL-8) on polymorphonuclear leukocyte (PMN) bactericidal function during normoxia. In these studies, we have investigated the effects of hypoxia +/- reoxygenation independently and with IL-1 beta, TNF-alpha, and IL-8 on PMN bactericidal activity. Hypoxia in and of itself did not significantly alter PMN bactericidal activity against Escherichia coli or Staphylcoccus aureus; however, after 2 h of reoxygenation (H/R), PMN bactericidal activity against E. coli was significantly reduced compared with levels seen after 2 h of hypoxia. Similar to what was observed during normoxia, TNF-alpha, IL-1 beta, and IL-8 increased PMN bactericidal activity during hypoxia compared with buffer control PMN for S. aureus but not E. coli after 4 h of hypoxia. Following H/R, neither TNF-alpha, IL-1 beta, nor IL-8 reversed the decline in bactericidal activity induced by reoxygenation alone. Monoclonal antibodies that blocked the functional epitope of particular cytokine receptors demonstrated that during both hypoxia and H/R IL-1 beta R type I, IL-8R type A, and TNF-alpha R p60 were the predominant receptors responsible for mediating the bactericidal effect of the cytokines. During hypoxia and H/R, the addition of exogenous cytokines did prevent the fall in bactericidal activity seen as PMN: target ratios decreased. The decline in bactericidal activity following H/R was mediated in part by reduced phagocytosis of serum-opsonized bacteria following H/R. These results demonstrated that oxidative stress in the form of hypoxia +/- reoxygenation independently modulate the effect of exogenously added cytokines on PMN bactericidal capability.
authors.affiliation: Brown University School of Medicine, Division of Surgical Research, Rhode Island Hospital, Providence 02903, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Simms
authors.forename: R
authors.initials: R
authors.lastname: D'Amico
mesh_terms: D001770:Blood Bactericidal Activity / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D018121:Receptors, Cytokine / Q000502:physiology; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D016209:Interleukin-8; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen