Alterations in the human lung proteome with lipopolysaccharide

被引:6
作者
Bowler R.P. [1 ]
Reisdorph N. [1 ]
Reisdorph R. [1 ]
Abraham E. [2 ]
机构
[1] Department of Medicine, National Jewish Health, Denver, CO
[2] Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
关键词
Acute Lung Injury; Idiopathic Pulmonary Fibrosis; Protein Spot; Drotrecogin Alfa; Gram Negative Sepsis;
D O I
10.1186/1471-2466-9-20
中图分类号
学科分类号
摘要
Background: Recombinant human activated protein C (rhAPC) is associated with improved survival in high-risk patients with severe sepsis; however, the effects of both lipopolysaccharide (LPS) and rhAPC on the bronchoalveolar lavage fluid (BALF) proteome are unknown. Methods: Using differential in gel electrophoresis (DIGE) we identified changes in the BALF proteome from 10 healthy volunteers given intrapulmonary LPS in one lobe and saline in another lobe. Subjects were randomized to pretreatment with saline or rhAPC. Results: An average of 255 protein spots were detected in each proteome. We found 31 spots corresponding to 8 proteins that displayed abundance increased or decreased at least 2-fold after LPS. Proteins that decreased after LPS included surfactant protein A, immunoglobulin J chain, fibrinogen-γ, α1-antitrypsin, immunoglobulin, and α2-HS-glycoprotein. Haptoglobin increased after LPS-treatment. Treatment with rhAPC was associated with a larger relative decrease in immunoglobulin J chain, fibrinogen-γ, α1-antitrypsin, and α2-HS-glycoprotein. Conclusion: Intrapulmonary LPS was associated with specific protein changes suggesting that the lung response to LPS is more than just a loss of integrity in the alveolar epithelial barrier; however, pretreatment with rhAPC resulted in minor changes in relative BALF protein abundance consistent with its lack of affect in ALI and milder forms of sepsis. © 2009 Bowler et al; licensee BioMed Central Ltd.
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[51]  
Bouchama A., Kunzelmann C., Dehbi M., Kwaasi A., Eldali A., Zobairi F., Freyssinet J.M., de Prost D., Recombinant activated protein C attenuates endothelial injury and inhibits procoagulant microparticles release in baboon heatstroke, Arterioscler Thromb Vasc Biol, 28, 7, pp. 1318-1325, (2008)
[52]  
Bernard G.R., Ely E.W., Wright T.J., Fraiz J., Stasek Jr. J.E., Russell J.A., Mayers I., Rosenfeld B.A., Morris P.E., Yan S.B., Helterbrand J.D., Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis, Crit Care Med, 29, 11, pp. 2051-2059, (2001)
[53]  
Shen L., Dahlback B., Villoutreix B.O., Tracking structural features leading to resistance of activated protein C to alpha 1-antitrypsin, Biochemistry, 39, 11, pp. 2853-2860, (2000)
[54]  
Glasscock L.N., Gerlitz B., Cooper S.T., Grinnell B.W., Church F.C., Basic residues in the 37-loop of activated protein C modulate inhibition by protein C inhibitor but not by alpha(1)-antitrypsin, Biochim Biophys Acta, 1649, 1, pp. 106-117, (2003)
[55]  
Abraham E., Laterre P.F., Garg R., Levy H., Talwar D., Trzaskoma B.L., Francois B., Guy J.S., Bruckmann M., Rea-Neto A., Rossaint R., Perrotin D., Sablotzki A., Arkins N., Utterback B.G., Macias W.L., Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death, N Engl J Med, 353, 13, pp. 1332-1341, (2005)
[56]  
Kotanidou A., Loutrari H., Papadomichelakis E., Glynos C., Magkou C., Armaganidis A., Papapetropoulos A., Roussos C., Orfanos S.E., Inhaled activated protein C attenuates lung injury induced by aerosolized endotoxin in mice, Vascul Pharmacol, 45, 2, pp. 134-140, (2006)
[57]  
Slofstra S.H., Groot A.P., Maris N.A., Reitsma P.H., Cate H.T., Spek C.A., Inhalation of activated protein C inhibits endotoxin-induced pulmonary inflammation in mice independent of neutrophil recruitment, Br J Pharmacol, 149, 6, pp. 740-746, (2006)
[58]  
MacLaren R., Stringer K.A., Emerging role of anticoagulants and fibrinolytics in the treatment of acute respiratory distress syndrome, Pharmacotherapy, 27, 6, pp. 860-873, (2007)
[59]  
Liu K.D., Levitt J., Zhuo H., Kallet R.H., Brady S., Steingrub J., Tidswell M., Siegel M.D., Soto G., Peterson M.W., Chesnutt M.S., Phillips C., Weinacker A., Thompson B.T., Eisner M.D., Matthay M.A., Randomized clinical trial of activated protein C for the treatment of acute lung injury, Am J Respir Crit Care Med, 178, 6, pp. 618-623, (2008)