Surfactant protein-d enhances phagocytosis and pulmonary clearance of respiratory syncytial virus.
Surfactant protein (SP)-D gene targeted (SP-D-/-) and wild-type mice were infected with respiratory syncytial virus (RSV) by intratracheal instillation. Decreased clearance of RSV was observed in SP-D-/- mice. Deficiency of SP-D was associated with increased inflammation and inflammatory cell recruitment in the lung after infection. In vitro, SP-D bound RSV-infected Vero cells. Binding was inhibited with ethylenediamine tetraacetic acid and maltose, suggesting that the carbohydrate recognition domain of SP-D recognizes RSV glycoproteins in a calcium-dependent manner. SP-D bound specifically to the RSV proteins G and F. Phagocytosis of RSV by alveolar macrophages was reduced in the absence of SP-D in vivo, and SP-D enhanced phagocytosis of RSV by alveolar macrophages and neutrophils but not peritoneal macrophages in vitro. Oxygen radical production by alveolar macrophages from SP-D+/+ and SP-D-/- mice was decreased after RSV infection, and SP-D ameliorated the inhibitory effects of RSV on oxygen radical production by macrophages and neutrophils in vitro. Because the airway is the usual portal of entry for RSV and other respiratory pathogens, the local production of SP-D is likely to play a role in innate defense responses to inhaled viruses.
LeVine
Ann Marie
AM
Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology and Critical Care Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. annmarie.levine@cchmc.org
Elliott
James
J
Whitsett
Jeffrey A
JA
Srikiatkhachorn
Anon
A
Crouch
Erika
E
DeSilva
Nihal
N
Korfhagen
Thomas
T
D000818:Animals; D002460:Cell Line; D005260:Female; D016676:Macrophages, Alveolar / Q000821:virology; D008297:Male; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012136:Respiratory Syncytial Viruses / Q000502:physiology*
D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins