Tumor Necrosis Factor α-Dependent Neutrophil Priming Prevents Intestinal Ischemia/Reperfusion-Induced Bacterial Translocation

Yen Zhen Lu, Ching-Ying Huang, Yi-Cheng Huang, Tsung-Chun Lee, Wei-Ting Kuo, Yu-Chen Pai, Linda Chia-Hui Yu

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


BACKGROUND: 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.

AIM: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: TNFα-primed neutrophils by HPC act as effectors cells for enhancing barrier integrity under gut ischemia.

Original languageEnglish
Pages (from-to)1498-1510
Number of pages13
JournalDigestive Diseases and Sciences
Issue number6
Publication statusPublished - Jun 2017
Externally publishedYes


  • Animals
  • Bacterial Translocation
  • Blood Bactericidal Activity
  • Cells, Cultured
  • Chemokine CXCL1/blood
  • Free Radicals/metabolism
  • Intestinal Mucosa/blood supply
  • Intestines/blood supply
  • Ischemic Preconditioning
  • Male
  • Neutrophil Activation
  • Neutrophils/physiology
  • Phagocytosis
  • Rats
  • Rats, Wistar
  • Recombinant Proteins/pharmacology
  • Reperfusion Injury/pathology
  • Respiratory Burst/drug effects
  • Tumor Necrosis Factor-alpha/blood


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