Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury

Heather E. Merry, Patrick S. Wolf, Elizabeth FitzSullivan, John C. Keech, Michael S. Mulligan

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: The availability of suitable lung donors has remained a significant barrier to lung transplantation. The clinical relevance of an isolated positive Gram stain in potential donor lungs, which occurs in >80%, is unclear. Low doses of lipopolysaccharide (LPS) have been protective in several models of ischemia-reperfusion injury through a pre-conditioning response. We sought to demonstrate that low-dose LPS is protective against subsequent lung ischemia-reperfusion injury. Methods: Pathogen-free Long-Evans rats were pre-treated with vehicle or LPS 24 hours before 90 minutes of ischemia and up to 4 hours of reperfusion. Lungs were assessed for vascular permeability, myeloperoxidase content, bronchoalveolar lavage inflammatory cell and cytokine/chemokine content, as well as nuclear translocation of nuclear factor κB (NFκB) and activator protein-1 (AP-1), and interleukin-1 receptor-associated kinase-1 (IRAK-1) and stress-activated protein kinase (SAPK) activation. Results: Compared with positive controls, LPS pre-treatment resulted in reductions in vascular permeability (70%, p < 0.001), myeloperoxidase content (93%, p < 0.001), bronchoalveolar lavage inflammatory cells (91%, p < 0.001), and inflammatory cytokine/chemokine content (cytokine-induced neutrophil chemoattractant, 99%, p = 0.003; interleukin-1β, 72%, p < 0.0001; tumor necrosis factor-α, 76%, p < 0.0001), NFκB (86%, p < 0.001) and AP-1 (97%, p < 0.001) nuclear translocation, and IRAK-1 (87%, p < 0.001) and SAPK (80%, p < 0.001) phosphorylation. Conclusions: Lipopolysaccharide pre-treatment reduced lung injury and inflammatory mediator production after subsequent exposure to ischemia-reperfusion. Understanding the clinical significance of lipopolysaccharide in donor lungs has the potential to expand and clarify donor inclusion criteria.

Original languageEnglish (US)
Pages (from-to)471-478
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2010

Fingerprint

Reperfusion Injury
Lipopolysaccharides
Lung
Interleukin-1 Receptor-Associated Kinases
Transcription Factor AP-1
Capillary Permeability
Bronchoalveolar Lavage
Cytokines
Heat-Shock Proteins
Chemokines
Protein Kinases
Peroxidase
Reperfusion
Ischemia
Long Evans Rats
Lung Transplantation
Chemotactic Factors
Lung Injury
Interleukin-1
Neutrophils

Keywords

  • TLR-4
  • lipopolysaccharide
  • lung ischemia-reperfusion injury
  • lung transplantation

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury. / Merry, Heather E.; Wolf, Patrick S.; FitzSullivan, Elizabeth; Keech, John C.; Mulligan, Michael S.

In: Journal of Heart and Lung Transplantation, Vol. 29, No. 4, 01.04.2010, p. 471-478.

Research output: Contribution to journalArticle

Merry, Heather E. ; Wolf, Patrick S. ; FitzSullivan, Elizabeth ; Keech, John C. ; Mulligan, Michael S. / Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury. In: Journal of Heart and Lung Transplantation. 2010 ; Vol. 29, No. 4. pp. 471-478.
@article{112a16622779435bbe42599e6763a4e8,
title = "Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury",
abstract = "Background: The availability of suitable lung donors has remained a significant barrier to lung transplantation. The clinical relevance of an isolated positive Gram stain in potential donor lungs, which occurs in >80{\%}, is unclear. Low doses of lipopolysaccharide (LPS) have been protective in several models of ischemia-reperfusion injury through a pre-conditioning response. We sought to demonstrate that low-dose LPS is protective against subsequent lung ischemia-reperfusion injury. Methods: Pathogen-free Long-Evans rats were pre-treated with vehicle or LPS 24 hours before 90 minutes of ischemia and up to 4 hours of reperfusion. Lungs were assessed for vascular permeability, myeloperoxidase content, bronchoalveolar lavage inflammatory cell and cytokine/chemokine content, as well as nuclear translocation of nuclear factor κB (NFκB) and activator protein-1 (AP-1), and interleukin-1 receptor-associated kinase-1 (IRAK-1) and stress-activated protein kinase (SAPK) activation. Results: Compared with positive controls, LPS pre-treatment resulted in reductions in vascular permeability (70{\%}, p < 0.001), myeloperoxidase content (93{\%}, p < 0.001), bronchoalveolar lavage inflammatory cells (91{\%}, p < 0.001), and inflammatory cytokine/chemokine content (cytokine-induced neutrophil chemoattractant, 99{\%}, p = 0.003; interleukin-1β, 72{\%}, p < 0.0001; tumor necrosis factor-α, 76{\%}, p < 0.0001), NFκB (86{\%}, p < 0.001) and AP-1 (97{\%}, p < 0.001) nuclear translocation, and IRAK-1 (87{\%}, p < 0.001) and SAPK (80{\%}, p < 0.001) phosphorylation. Conclusions: Lipopolysaccharide pre-treatment reduced lung injury and inflammatory mediator production after subsequent exposure to ischemia-reperfusion. Understanding the clinical significance of lipopolysaccharide in donor lungs has the potential to expand and clarify donor inclusion criteria.",
keywords = "TLR-4, lipopolysaccharide, lung ischemia-reperfusion injury, lung transplantation",
author = "Merry, {Heather E.} and Wolf, {Patrick S.} and Elizabeth FitzSullivan and Keech, {John C.} and Mulligan, {Michael S.}",
year = "2010",
month = "4",
day = "1",
doi = "10.1016/j.healun.2009.11.005",
language = "English (US)",
volume = "29",
pages = "471--478",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "Elsevier USA",
number = "4",

}

TY - JOUR

T1 - Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury

AU - Merry, Heather E.

AU - Wolf, Patrick S.

AU - FitzSullivan, Elizabeth

AU - Keech, John C.

AU - Mulligan, Michael S.

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Background: The availability of suitable lung donors has remained a significant barrier to lung transplantation. The clinical relevance of an isolated positive Gram stain in potential donor lungs, which occurs in >80%, is unclear. Low doses of lipopolysaccharide (LPS) have been protective in several models of ischemia-reperfusion injury through a pre-conditioning response. We sought to demonstrate that low-dose LPS is protective against subsequent lung ischemia-reperfusion injury. Methods: Pathogen-free Long-Evans rats were pre-treated with vehicle or LPS 24 hours before 90 minutes of ischemia and up to 4 hours of reperfusion. Lungs were assessed for vascular permeability, myeloperoxidase content, bronchoalveolar lavage inflammatory cell and cytokine/chemokine content, as well as nuclear translocation of nuclear factor κB (NFκB) and activator protein-1 (AP-1), and interleukin-1 receptor-associated kinase-1 (IRAK-1) and stress-activated protein kinase (SAPK) activation. Results: Compared with positive controls, LPS pre-treatment resulted in reductions in vascular permeability (70%, p < 0.001), myeloperoxidase content (93%, p < 0.001), bronchoalveolar lavage inflammatory cells (91%, p < 0.001), and inflammatory cytokine/chemokine content (cytokine-induced neutrophil chemoattractant, 99%, p = 0.003; interleukin-1β, 72%, p < 0.0001; tumor necrosis factor-α, 76%, p < 0.0001), NFκB (86%, p < 0.001) and AP-1 (97%, p < 0.001) nuclear translocation, and IRAK-1 (87%, p < 0.001) and SAPK (80%, p < 0.001) phosphorylation. Conclusions: Lipopolysaccharide pre-treatment reduced lung injury and inflammatory mediator production after subsequent exposure to ischemia-reperfusion. Understanding the clinical significance of lipopolysaccharide in donor lungs has the potential to expand and clarify donor inclusion criteria.

AB - Background: The availability of suitable lung donors has remained a significant barrier to lung transplantation. The clinical relevance of an isolated positive Gram stain in potential donor lungs, which occurs in >80%, is unclear. Low doses of lipopolysaccharide (LPS) have been protective in several models of ischemia-reperfusion injury through a pre-conditioning response. We sought to demonstrate that low-dose LPS is protective against subsequent lung ischemia-reperfusion injury. Methods: Pathogen-free Long-Evans rats were pre-treated with vehicle or LPS 24 hours before 90 minutes of ischemia and up to 4 hours of reperfusion. Lungs were assessed for vascular permeability, myeloperoxidase content, bronchoalveolar lavage inflammatory cell and cytokine/chemokine content, as well as nuclear translocation of nuclear factor κB (NFκB) and activator protein-1 (AP-1), and interleukin-1 receptor-associated kinase-1 (IRAK-1) and stress-activated protein kinase (SAPK) activation. Results: Compared with positive controls, LPS pre-treatment resulted in reductions in vascular permeability (70%, p < 0.001), myeloperoxidase content (93%, p < 0.001), bronchoalveolar lavage inflammatory cells (91%, p < 0.001), and inflammatory cytokine/chemokine content (cytokine-induced neutrophil chemoattractant, 99%, p = 0.003; interleukin-1β, 72%, p < 0.0001; tumor necrosis factor-α, 76%, p < 0.0001), NFκB (86%, p < 0.001) and AP-1 (97%, p < 0.001) nuclear translocation, and IRAK-1 (87%, p < 0.001) and SAPK (80%, p < 0.001) phosphorylation. Conclusions: Lipopolysaccharide pre-treatment reduced lung injury and inflammatory mediator production after subsequent exposure to ischemia-reperfusion. Understanding the clinical significance of lipopolysaccharide in donor lungs has the potential to expand and clarify donor inclusion criteria.

KW - TLR-4

KW - lipopolysaccharide

KW - lung ischemia-reperfusion injury

KW - lung transplantation

UR - http://www.scopus.com/inward/record.url?scp=77949570288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949570288&partnerID=8YFLogxK

U2 - 10.1016/j.healun.2009.11.005

DO - 10.1016/j.healun.2009.11.005

M3 - Article

C2 - 20044277

AN - SCOPUS:77949570288

VL - 29

SP - 471

EP - 478

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

SN - 1053-2498

IS - 4

ER -