The lectin-like doMain of tumor necrosis factor improves lung function after rat lung transplantation-Potential role for a reduction in reactive oxygen species generation

Jürg Hamacher, Uz Stammberger, Jeremie Roux, Sanjiv Kumar, Guang Yang, Chenling Xiong, Ralph A. Schmid, Richard M. Fakin, Trinad Chakraborty, Hamid M.D. Hossain, Jean François Pittet, Albrecht Wendel, Stephen Matthew Black, Rudolf Lucas

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objective: To test the hypothesis that the lectin-like doMain of tumor necrosis factor, mimicked by the TIP peptide, can improve lung function after unilateral orthotopic lung isotransplantation. Because of a lack of a specific treatment for ischemia reperfusion-mediated lung injury, accompanied by a disrupted barrier integrity and a dysfunctional alveolar liquid clearance, alternative therapies restoring these parameters after lung transplantation are required. Design: Prospective, randomized laboratory investigation. Setting: University-affiliated laboratory. Subjects: Adult female rats. Interventions: Tuberoinfundibular peptide, mimicking the lectin-like doMain of tumor necrosis factor, mutant TIP peptide, N,N′-diacetylchitobiose/TIP peptide, and amiloride/TIP peptide were instilled intratracheally in the left lung immediately before the isotransplantation was performed. An additional group received an intravenous TIP peptide treatment, 1.5 mins before transplantation. Studies using isolated rat type II alveolar epithelial cell monolayers and ovine pulmonary endothelial cells were also performed. Measurements and Main Results: Intratracheal pretreatment of the transplantable left lung with the TIP peptide, but not with an inactive mutant TIP peptide, resulted in significantly improved oxygenation 24 hrs after transplantation. This treatment led to a significantly reduced neutrophil content in the lavage fluid. Both the effects on oxygenation and neutrophil infiltration were inhibited by the epithelial sodium channel blocker amiloride. The TIP peptide blunted reactive oxygen species production in pulmonary artery endothelial cells under hypoxia and reoxygenation and reduced reactive oxygen species content in the transplanted rat lungs in vivo. Ussing chamber experiments using monolayers of primary type II rat pneumocytes indicated that the primary site of action of the peptide was on the apical side of these cells. Conclusions: These data demonstrate that the TIP peptide significantly improves lung function after lung transplantation in the rat, in part, by reducing neutrophil content and reactive oxygen species generation. These studies suggest that the TIP peptide is a potential therapeutic agent against the ischemia reperfusion injury associated with lung transplantation.

Original languageEnglish (US)
Pages (from-to)871-878
Number of pages8
JournalCritical care medicine
Volume38
Issue number3
DOIs
StatePublished - Jan 1 2010

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Lung Transplantation
Lectins
Reactive Oxygen Species
Tumor Necrosis Factor-alpha
Lung
Peptides
Alveolar Epithelial Cells
Amiloride
Epithelial Sodium Channel Blockers
Neutrophils
Endothelial Cells
Transplantation
Cell Hypoxia
Neutrophil Infiltration
Therapeutic Irrigation
Lung Injury
Therapeutics
Complementary Therapies
Reperfusion Injury
Pulmonary Artery

Keywords

  • Lung transplantation
  • Pulmonary edema
  • Rat
  • Reperfusion injury
  • Sheep
  • Therapeutics
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

The lectin-like doMain of tumor necrosis factor improves lung function after rat lung transplantation-Potential role for a reduction in reactive oxygen species generation. / Hamacher, Jürg; Stammberger, Uz; Roux, Jeremie; Kumar, Sanjiv; Yang, Guang; Xiong, Chenling; Schmid, Ralph A.; Fakin, Richard M.; Chakraborty, Trinad; Hossain, Hamid M.D.; Pittet, Jean François; Wendel, Albrecht; Black, Stephen Matthew; Lucas, Rudolf.

In: Critical care medicine, Vol. 38, No. 3, 01.01.2010, p. 871-878.

Research output: Contribution to journalArticle

Hamacher, J, Stammberger, U, Roux, J, Kumar, S, Yang, G, Xiong, C, Schmid, RA, Fakin, RM, Chakraborty, T, Hossain, HMD, Pittet, JF, Wendel, A, Black, SM & Lucas, R 2010, 'The lectin-like doMain of tumor necrosis factor improves lung function after rat lung transplantation-Potential role for a reduction in reactive oxygen species generation', Critical care medicine, vol. 38, no. 3, pp. 871-878. https://doi.org/10.1097/CCM.0b013e3181cdf725
Hamacher, Jürg ; Stammberger, Uz ; Roux, Jeremie ; Kumar, Sanjiv ; Yang, Guang ; Xiong, Chenling ; Schmid, Ralph A. ; Fakin, Richard M. ; Chakraborty, Trinad ; Hossain, Hamid M.D. ; Pittet, Jean François ; Wendel, Albrecht ; Black, Stephen Matthew ; Lucas, Rudolf. / The lectin-like doMain of tumor necrosis factor improves lung function after rat lung transplantation-Potential role for a reduction in reactive oxygen species generation. In: Critical care medicine. 2010 ; Vol. 38, No. 3. pp. 871-878.
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