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Anionic Pulmonary Surfactant Lipids Suppress Respiratory Syncytial Virus Infection

¹ Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Mari Nakamura, M.D., Ph.D., Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: nakamuram{at}njc.org

The changes in surfactant phospholipids of lungs, especially the minor surfactant phospholipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG), correlates with the pathogenesis of pulmonary diseases, acute respiratory disease (ARDS), interstitial lung disease (ILD), and bronchial asthma. We have recently discovered that POPG has broad inhibitory effects on proinflammatory cytokine production (IL-6, IL-8) induced by multiple TLR agonists (TLR1/2, TLR3, TLR4, TLR2/6, TLR7/8) in bronchial epithelium. Respiratory syncytial virus (RSV) is the most common cause of hospitalization for respiratory illness in young children and RSV infection is one major cause of acute exacerbation of asthma. The aim of this study was to determine the function of surfactant lipids, especially POPG, to RSV infection. We estimated the effects of POPG on human bronchial epithelial cells (Beas2B and primary cells [NHBE]), with RSV infection. Pretreatment with POPG significantly blocked viral infection and proinflammatory cytokine (IL-6, IL-8) production and cytopathic effects induced by RSV in bronchial epithelial cells. Direct binding measurements showed that RSV interacts with CD14, and POPG markedly inhibits this interaction by binding both virus and the protein. To determine POPG has inhibitory effects in vivo, we infected BALB/c mice with RSV. POPG treatment markedly attenuated RSV titer in the lung and lung inflammation in histopathology. These findings demonstrate a potent anti RSV function for POPG and raise the possibility of its use to treat infections and pulmonary disease.

FOOTNOTES

Conflict of Interest Statement: M.N. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. H.W.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.N. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. A.E. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. E.D.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.R.V. and the National Jewish Medical and Research Center have filed a patent for using unsaturated anionic lipids as TLR antagonists and antiviral agents.

(Received in original form November 19, 2008; accepted in final form November 19, 2008)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nakamura, M. Articles by Voelker, D. R. Search for Related Content PubMed Articles by Nakamura, M. Articles by Voelker, D. R.