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

Heather E MERRY; Patrick S WOLF; Elizabeth FITZSULLIVAN; John C KEECH; Michael S MULLIGAN

doi:10.1016/j.healun.2009.11.005

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

Journal article

Peer reviewed

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

Heather E MERRY, Patrick S WOLF, Elizabeth FITZSULLIVAN, John C KEECH and Michael S MULLIGAN

The Journal of heart and lung transplantation, Vol.29(4), pp.471-478

2010

DOI: 10.1016/j.healun.2009.11.005

PMCID: PMC3052281

PMID: 20044277

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https://www.ncbi.nlm.nih.gov/pmc/articles/3052281View

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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 kappaB (NFkappaB) 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-1beta, 72%, p < 0.0001; tumor necrosis factor-alpha, 76%, p < 0.0001), NFkappaB (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.

Cardiology. Vascular system

Biological and medical sciences

Medical sciences

Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases

Surgery of the heart

Details

Title: Subtitle: Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury
Creators: Heather E MERRY - Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington, United States
Patrick S WOLF - Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington, United States
Elizabeth FITZSULLIVAN - Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington, United States
John C KEECH - Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington, United States
Michael S MULLIGAN - Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington, United States
Resource Type: Journal article
Publication Details: The Journal of heart and lung transplantation, Vol.29(4), pp.471-478
DOI: 10.1016/j.healun.2009.11.005
PMID: 20044277
PMCID: PMC3052281
NLM abbreviation: J Heart Lung Transplant
ISSN: 1053-2498
eISSN: 1557-3117
Publisher: Elsevier; New York, NY
Language: English
Date published: 2010
Academic Unit: Surgery; Cardiothoracic Surgery
Record Identifier: 9984051524502771

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