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

• Published in: Digestive diseases and sciences 2017-06, Vol.62 (6), p.1498-1510
• Main Authors: Lu, Yen-Zhen, Huang, Ching-Ying, Huang, Yi-Cheng, Lee, Tsung-Chun, Kuo, Wei-Ting, Pai, Yu-Chen, Yu, Linda Chia-Hui
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Translocation; Biochemistry; Blood Bactericidal Activity; Cells, Cultured; Chemokine CXCL1 - blood; Chemokine CXCL1 - pharmacology; Free Radicals - metabolism; Gastroenterology; Hepatology; Intestinal Mucosa - blood supply; Intestinal Mucosa - pathology; Intestines - blood supply; Intestines - microbiology; Ischemic Preconditioning; Male; Medicine; Medicine & Public Health; Neutrophil Activation; Neutrophils - physiology; Neutrophils - transplantation; Oncology; Original Article; Phagocytosis; Rats; Rats, Wistar; Recombinant Proteins - pharmacology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Respiratory Burst - drug effects; Transplant Surgery; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-017-4468-3

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.