Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus-induced inflammation and infection.
Respiratory syncytial virus (RSV) is the most common cause of hospitalization for respiratory tract infection in young children. It is also a significant cause of morbidity and mortality in elderly individuals and in persons with asthma and chronic obstructive pulmonary disease. Currently, no reliable vaccine or simple RSV antiviral therapy is available. Recently, we determined that the minor pulmonary surfactant phospholipid, palmitoyl-oleoyl-phosphatidylglycerol (POPG), could markedly attenuate inflammatory responses induced by lipopolysaccharide through direct interactions with the Toll-like receptor 4 (TLR4) interacting proteins CD14 and MD-2. CD14 and TLR4 have been implicated in the host response to RSV. Treatment of bronchial epithelial cells with POPG significantly inhibited interleukin-6 and -8 production, as well as the cytopathic effects induced by RSV. The phospholipid bound RSV with high affinity and inhibited viral attachment to HEp2 cells. POPG blocked viral plaque formation in vitro by 4 log units, and markedly suppressed the expansion of plaques from cells preinfected with the virus. Administration of POPG to mice, concomitant with viral infection, almost completely eliminated the recovery of virus from the lungs at 3 and 5 days after infection, and abrogated IFN-gamma (IFN-gamma) production and the enhanced expression of surfactant protein D (SP-D). These findings demonstrate an important approach to prevention and treatment of RSV infections using exogenous administration of a specific surfactant phospholipid.
Numata
Mari
M
Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO 80206, USA.
Chu
Hong Wei
HW
Dakhama
Azzeddine
A
Voelker
Dennis R
DR
D000818:Animals; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010715:Phosphatidylglycerols / Q000494:pharmacology* / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000494:pharmacology* / Q000627:therapeutic use; D020545:Respiratory Mucosa / Q000166:cytology; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol