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

作者：Dorr Anthony D; Wilson Michael R; Wakabayashi Kenji; Waite Alicia C; Patel Brijesh V; van Rooijen Nico; O'Dea Kieran P; Takata Masao^*

来源：Journal of Applied Physiology, 2011, 111(1): 177-184.

DOI：10.1152/japplphysiol.00007.2011

• lipopolysaccharide
• pulmonary edema
• pulmonary inflammation
• ventilator-induced lung injury

Dorr AD, Wilson MR, Wakabayashi K, Waite AC, Patel BV, van Rooijen N, O'Dea KP, Takata M. Sources of alveolar soluble TNF receptors during acute lung injury of different etiologies. J Appl Physiol 111: 177-184, 2011. First published April 21, 2011; 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 intra-alveolar 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 intra-alveolar 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 intra-alveolar sTNFR levels during ALI and may suggest sTNFRs as potential markers for evaluating the pathophysiology of ALI.

• 出版日期2011-7