Dynamic regulation of cardiolipin by the lipid pump, ATP8b1, determines the severity of lung injury in experimental bacterial pneumonia

Pneumonia remains the leading cause of infectious deaths and yet fundamentally new conceptual models underlying its pathogenesis have not emerged. Patients and mice with bacterial pneumonia have marked elevations of cardiolipin in lung fluid, a rare, mitochondrial-specific phospholipid that potently disrupts surfactant function. Intratracheal cardiolipin in mice recapitulates the clinical Users may view, print, copy, download and text and datamine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Address Correspondence to: Rama K. Mallampalli, M.D., Department of Internal Medicine, PACCM, NW628 Montefiore, 3459 Fifth Avenue, Pittsburgh, PA 15213, Telephone: 412-692-2112, Fax: 412-692-2260, [email protected]. Author Contributions N.B.R designed and executed CL-ATP8b1 binding, in vitro imaging, immunological studies, and wrote the manuscript. L.D. edited the manuscript, conducted the human studies. B.B.C. performed in vitro (CL uptake, biochemical and molecular) experiments, and all animal studies. B.J.M. and M.D. contributed to human studies and statistical analyses. A.K.W., T.A.C., M.A., P.L.B., F.C.H., S.N.M. performed in vitro studies. A.J. R. and C.P.O. performed mouse studies. D.M., E.H-R., and C.E. conducted CL analysis. L.G. conducted surfactant studies. J.C.S. and G.M. designed and conducted in vivo imaging. V.E.K. designed and executed mass spectrometry of CL with assistance from Y.Y.T. and V.E.K provided editorial suggestions. R.K.M. revised the manuscript and directed the study. Competing financial interests The authors declare no competing financial interests. HHS Public Access Author manuscript Nat Med. Author manuscript; available in PMC 2015 July 13. Published in final edited form as: Nat Med. 2010 October ; 16(10): 1120–1127. doi:10.1038/nm.2213. A uhor M anscript