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Sources of alveolar soluble TNF receptors during acute lung injury of different etiologies.

Authors: Dorr, AD  Wilson, MR  Wakabayashi, K  Waite, AC  Patel, BV  Van Rooijen, N  O'Dea, KP  Takata, M 
Citation: Dorr AD, etal., J Appl Physiol. 2011 Apr 21.
Pubmed: (View Article at PubMed) PMID:21512145
DOI: Full-text: DOI:10.1152/japplphysiol.00007.2011

Elevated soluble tumor necrosis factor-alpha receptor (sTNFR) levels in bronchoalveolar lavage fluid (BALF) are associated with poor patient outcome in acute lung injury (ALI). The mechanisms underlying these increases are unknown, but it is possible that pulmonary inflammation and increased alveolar epithelial permeability may individually contribute. We investigated mechanisms of elevated BALF sTNFRs in two in vivo mouse models of ALI. Anesthetized mice were challenged with intratracheal lipopolysaccharide or subjected to injurious mechanical ventilation. Lipopolysaccharide instillation produced acute intraalveolar inflammation, but minimal alveolar epithelial permeability changes, with increased BALF sTNFR p75, but not p55. Increased p75 levels were markedly attenuated by alveolar macrophage depletion. In contrast, injurious ventilation induced substantial alveolar epithelial permeability, with increased BALF p75 and p55, which strongly correlated with total protein. BALF sTNFRs were not increased in isolated buffer-perfused lungs (devoid of circulating sTNFRs) subjected to injurious ventilation. These results suggest that lipopolysaccharide-induced intraalveolar inflammation upregulates alveolar macrophage-mediated production of sTNFR p75, whereas enhanced alveolar epithelial permeability following mechanical ventilation leads to increased BALF p75 and p55 via plasma leakage. These data provide new insights into differential regulation of intraalveolar sTNFR levels during ALI, and may suggest sTNFRs as potential markers for evaluating the pathophysiology of ALI.

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RGD Object Information
RGD ID: 5131206
Created: 2011-04-25
Species: All species
Last Modified: 2011-04-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.