Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.

<h4>Background</h4>Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Since Toll-like receptors (TLR) act as sensors of tissue injury as well as micr...

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Autores principales: Diego C Reino, Vadim Pisarenko, David Palange, Danielle Doucet, Robert P Bonitz, Qi Lu, Iriana Colorado, Sharvil U Sheth, Benjamin Chandler, Kolenkode B Kannan, Madhuri Ramanathan, Da Zhong Xu, Edwin A Deitch, Rena Feinman
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:14c935ccf42d4031b16d9051dee8602b2021-11-18T06:48:42ZTrauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.1932-620310.1371/journal.pone.0014829https://doaj.org/article/14c935ccf42d4031b16d9051dee8602b2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829592/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Since Toll-like receptors (TLR) act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R) injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS) mediate gut-induced lung injury via TLR4 activation.<h4>Methods/principal findings</h4>The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT) mice induced lung injury. Using C3H/HeJ mice that harbor a TLR4 mutation, we found that TLR4 activation was necessary for the development of T/HS porcine lymph-induced lung injury as determined by Evan's blue dye (EBD) lung permeability and myeloperoxidase (MPO) levels as well as the induction of the injurious pulmonary iNOS response. TRIF and Myd88 deficiency fully and partially attenuated T/HS lymph-induced increases in lung permeability respectively. Additional studies in TLR2 deficient mice showed that TLR2 activation was not involved in the pathology of T/HS lymph-induced lung injury. Lastly, the lymph samples were devoid of bacteria, endotoxin and bacterial DNA and passage of lymph through an endotoxin removal column did not abrogate the ability of T/HS lymph to cause lung injury in naïve mice.<h4>Conclusions/significance</h4>Our findings suggest that non-microbial factors in the intestinal mesenteric lymph after T/HS are capable of recreating T/HS-induced lung injury via TLR4 activation.Diego C ReinoVadim PisarenkoDavid PalangeDanielle DoucetRobert P BonitzQi LuIriana ColoradoSharvil U ShethBenjamin ChandlerKolenkode B KannanMadhuri RamanathanDa Zhong XuEdwin A DeitchRena FeinmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e14829 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Diego C Reino
Vadim Pisarenko
David Palange
Danielle Doucet
Robert P Bonitz
Qi Lu
Iriana Colorado
Sharvil U Sheth
Benjamin Chandler
Kolenkode B Kannan
Madhuri Ramanathan
Da Zhong Xu
Edwin A Deitch
Rena Feinman
Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.
description <h4>Background</h4>Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Since Toll-like receptors (TLR) act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R) injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS) mediate gut-induced lung injury via TLR4 activation.<h4>Methods/principal findings</h4>The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT) mice induced lung injury. Using C3H/HeJ mice that harbor a TLR4 mutation, we found that TLR4 activation was necessary for the development of T/HS porcine lymph-induced lung injury as determined by Evan's blue dye (EBD) lung permeability and myeloperoxidase (MPO) levels as well as the induction of the injurious pulmonary iNOS response. TRIF and Myd88 deficiency fully and partially attenuated T/HS lymph-induced increases in lung permeability respectively. Additional studies in TLR2 deficient mice showed that TLR2 activation was not involved in the pathology of T/HS lymph-induced lung injury. Lastly, the lymph samples were devoid of bacteria, endotoxin and bacterial DNA and passage of lymph through an endotoxin removal column did not abrogate the ability of T/HS lymph to cause lung injury in naïve mice.<h4>Conclusions/significance</h4>Our findings suggest that non-microbial factors in the intestinal mesenteric lymph after T/HS are capable of recreating T/HS-induced lung injury via TLR4 activation.
format article
author Diego C Reino
Vadim Pisarenko
David Palange
Danielle Doucet
Robert P Bonitz
Qi Lu
Iriana Colorado
Sharvil U Sheth
Benjamin Chandler
Kolenkode B Kannan
Madhuri Ramanathan
Da Zhong Xu
Edwin A Deitch
Rena Feinman
author_facet Diego C Reino
Vadim Pisarenko
David Palange
Danielle Doucet
Robert P Bonitz
Qi Lu
Iriana Colorado
Sharvil U Sheth
Benjamin Chandler
Kolenkode B Kannan
Madhuri Ramanathan
Da Zhong Xu
Edwin A Deitch
Rena Feinman
author_sort Diego C Reino
title Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.
title_short Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.
title_full Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.
title_fullStr Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.
title_full_unstemmed Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.
title_sort trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced tlr4 pathway in mice.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/14c935ccf42d4031b16d9051dee8602b
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