PMID- 33042165
OWN - NLM
STAT- MEDLINE
DCOM- 20210614
LR  - 20240429
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Gut Ischemia Reperfusion Injury Induces Lung Inflammation via Mesenteric 
      Lymph-Mediated Neutrophil Activation.
PG  - 586685
LID - 10.3389/fimmu.2020.586685 [doi]
LID - 586685
AB  - Gut ischemia/reperfusion (I/R) injury is a common clinical problem associated 
      with significant mortality and morbidities that result from systemic inflammation 
      and remote organ dysfunction, typically acute lung injury. The mechanisms 
      underlying the dissemination of gut-derived harmful mediators into the 
      circulation are poorly understood. The objective of our study was to determine 
      the role of mesenteric lymphatic circulation in the systemic and pulmonary 
      inflammatory response to gut I/R. Using a murine intestinal I/R model, we 
      evaluated whether and how blocking mesenteric lymph flow affects the inflammatory 
      response in local tissues (gut) and remote organs (lungs). We further explored 
      the mechanisms of post-I/R lymph-induced systemic inflammation by examining 
      neutrophil activity and interaction with endothelial cells in vitro. Mice 
      subjected to intestinal I/R displayed a significant inflammatory response in 
      local tissues, evidenced by neutrophil infiltration into mucosal areas, as well 
      as lung inflammation, evidenced by increased myeloperoxidase levels, neutrophil 
      infiltration, and elevated microvascular permeability in the lungs. Mesenteric 
      lymph duct ligation (MLDL) had no effect on gut injury per se, but effectively 
      attenuated lung injury following gut I/R. Cell experiments showed that lymph 
      fluid from post-I/R animals, but not pre-I/R, increased neutrophil surface CD11b 
      expression and their ability to migrate across vascular endothelial monolayers. 
      Moreover, post-I/R lymph upregulated neutrophil expression of pro-inflammatory 
      cytokines and chemokines, which was mediated by a mechanism involving nuclear 
      factor (NF)-kappaB signaling. Consistently, gut I/R activated NF-kappaB in lung 
      neutrophils, which was alleviated by MLDL. In conclusion, all these data indicate 
      that mesenteric lymph circulation contributes to neutrophil activation and lung 
      inflammation following gut I/R injury partly through activating NF-kappaB.
CI  - Copyright (c) 2020 Ma, Zabell, Creasy, Yang, Chatterjee, Villalba, Kistler, Wu and 
      Yuan.
FAU - Ma, Yonggang
AU  - Ma Y
AD  - Department of Molecular Pharmacology and Physiology, University of South Florida 
      Morsani College of Medicine, Tampa, FL, United States.
FAU - Zabell, Taylor
AU  - Zabell T
AD  - Department of Molecular Pharmacology and Physiology, University of South Florida 
      Morsani College of Medicine, Tampa, FL, United States.
FAU - Creasy, Alexandra
AU  - Creasy A
AD  - Department of Molecular Pharmacology and Physiology, University of South Florida 
      Morsani College of Medicine, Tampa, FL, United States.
FAU - Yang, Xiaoyuan
AU  - Yang X
AD  - Department of Molecular Pharmacology and Physiology, University of South Florida 
      Morsani College of Medicine, Tampa, FL, United States.
FAU - Chatterjee, Victor
AU  - Chatterjee V
AD  - Department of Molecular Pharmacology and Physiology, University of South Florida 
      Morsani College of Medicine, Tampa, FL, United States.
FAU - Villalba, Nuria
AU  - Villalba N
AD  - Department of Molecular Pharmacology and Physiology, University of South Florida 
      Morsani College of Medicine, Tampa, FL, United States.
FAU - Kistler, Erik B
AU  - Kistler EB
AD  - Department of Anesthesiology and Critical Care, University of California, San 
      Diego, Veterans Affairs San Diego Healthcare System, San Diego, CA, United 
      States.
FAU - Wu, Mack H
AU  - Wu MH
AD  - Department of Surgery, University of South Florida Morsani College of Medicine, 
      Tampa, FL, United States.
AD  - James A. Haley Veterans' Hospital, Tampa, FL, United States.
FAU - Yuan, Sarah Y
AU  - Yuan SY
AD  - Department of Molecular Pharmacology and Physiology, University of South Florida 
      Morsani College of Medicine, Tampa, FL, United States.
AD  - Department of Surgery, University of South Florida Morsani College of Medicine, 
      Tampa, FL, United States.
LA  - eng
GR  - R35 HL150732/HL/NHLBI NIH HHS/United States
GR  - R01 HL120954/HL/NHLBI NIH HHS/United States
GR  - I01 BX000799/BX/BLRD VA/United States
GR  - IK6 BX004210/BX/BLRD VA/United States
GR  - R01 GM097270/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200911
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
SB  - IM
MH  - Animals
MH  - Intestines/immunology/injuries/pathology
MH  - Lymphatic System/*immunology
MH  - Male
MH  - Mesentery/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neutrophil Activation/*immunology
MH  - Pneumonia/*immunology/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*immunology/metabolism
PMC - PMC7517702
OTO - NOTNLM
OT  - acute lung injury
OT  - inflammation
OT  - intestinal ischemia/reperfusion
OT  - mesenteric lymph
OT  - neutrophils
OT  - permeability
EDAT- 2020/10/13 06:00
MHDA- 2021/06/16 06:00
PMCR- 2020/01/01
CRDT- 2020/10/12 05:29
PHST- 2020/07/23 00:00 [received]
PHST- 2020/08/21 00:00 [accepted]
PHST- 2020/10/12 05:29 [entrez]
PHST- 2020/10/13 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.586685 [doi]
PST - epublish
SO  - Front Immunol. 2020 Sep 11;11:586685. doi: 10.3389/fimmu.2020.586685. eCollection 
      2020.