title: Tumor Necrosis Factor α-Dependent Neutrophil Priming Prevents Intestinal Ischemia/Reperfusion-Induced Bacterial Translocation.
abstract: Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. Protection against I/R injury in sterile organs by hypoxic preconditioning (HPC) had been attributed to erythropoietic and angiogenic responses. Our previous study showed attenuation of intestinal I/R injury by HPC for 21 days in a neutrophil-dependent manner.
  
  
  
  To investigate the underlying mechanisms of neutrophil priming by HPC, and explore whether adoptive transfer of primed neutrophils is sufficient to ameliorate intestinal I/R injury.
  
  
  
  Rats raised in normoxia (NM) and HPC for 3 or 7 days were subjected to sham operation or superior mesenteric artery occlusion for I/R challenge. Neutrophils isolated from rats raised in NM or HPC for 21 days were intravenously injected into naïve controls prior to I/R.
  
  
  
  Similar to the protective effect of HPC-21d, I/R-induced mucosal damage was attenuated by HPC-7d but not by HPC-3d. Naïve rats reconstituted with neutrophils of HPC-21d rats showed increase in intestinal phagocytic infiltration and myeloperoxidase activity, and barrier protection against I/R insult. Elevated free radical production, and higher bactericidal and phagocytic activity were observed in HPC neutrophils compared to NM controls. Moreover, increased serum levels of tumor necrosis factor α (TNFα) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were seen in HPC rats. Naïve neutrophils incubated with HPC serum or recombinant TNFα, but not CINC-1, exhibited heightened respiratory burst and bactericidal activity. Lastly, neutrophil priming effect was abolished by neutralization of TNFα in HPC serum.
  
  
  
  TNFα-primed neutrophils by HPC act as effectors cells for enhancing barrier integrity under gut ischemia.
authors.affiliation: Graduate Institute of Physiology, National Taiwan University College of Medicine, Suite 1020, #1 Jen-Ai Rd. Sec. I, Taipei 100, Taiwan, ROC.
authors.forename: Yen-Zhen
authors.initials: YZ
authors.lastname: Lu
authors.affiliation: Graduate Institute of Physiology, National Taiwan University College of Medicine, Suite 1020, #1 Jen-Ai Rd. Sec. I, Taipei 100, Taiwan, ROC.
authors.forename: Ching-Ying
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Graduate Institute of Physiology, National Taiwan University College of Medicine, Suite 1020, #1 Jen-Ai Rd. Sec. I, Taipei 100, Taiwan, ROC.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Graduate Institute of Physiology, National Taiwan University College of Medicine, Suite 1020, #1 Jen-Ai Rd. Sec. I, Taipei 100, Taiwan, ROC.|Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Tsung-Chun
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Physiology, National Taiwan University College of Medicine, Suite 1020, #1 Jen-Ai Rd. Sec. I, Taipei 100, Taiwan, ROC.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Physiology, National Taiwan University College of Medicine, Suite 1020, #1 Jen-Ai Rd. Sec. I, Taipei 100, Taiwan, ROC.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Pai
authors.affiliation: Graduate Institute of Physiology, National Taiwan University College of Medicine, Suite 1020, #1 Jen-Ai Rd. Sec. I, Taipei 100, Taiwan, ROC. lchyu@ntu.edu.tw.
authors.forename: Linda Chia-Hui
authors.identifier: 0000-0003-1461-3249
authors.initials: LC
authors.lastname: Yu
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D001770:Blood Bactericidal Activity; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000097:blood / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000473:pathology; D007422:Intestines / Q000098:blood supply / Q000382:microbiology; D019194:Ischemic Preconditioning; D008297:Male; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology* / Q000637:transplantation*; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D016897:Respiratory Burst / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000494:pharmacology
chemical_list: D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D005609:Free Radicals; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: Bacterial influx; Epithelial barrier; Intermittent hypoxia; Intestinal ischemia; Neutrophil activity; Tumor necrosis factor