Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

Eur J Immunol. 2003 Oct;33(10):2894-902. doi: 10.1002/eji.200324218.

Abstract

Surfactant protein A (SP-A) and lactoferrin (LF) play important roles in innate immune systems in the respiratory mucous membranes. We investigated how SP-A and LF act against respiratory syncytial virus (RSV) infection. The present study indicated that RSV-induced IL-8 secretion from HEp-2 cells was up-regulated by SP-A (170% of control) but down-regulated by LF (23% of control). RSV infectivity determined by viral titers and the uptake of FITC-labeled RSV were also increased by SP-A, but decreased by LF. To clarify the mechanism of these opposite effects, we examined the interactions of SP-A and LF with RSV F protein, the most important surface glycoprotein for viral penetration. RSV F protein was found to be the ligand for both SP-A and LF, but the manners of binding were different. LF directly interacted with the F(1) subunit, which involved antigenic sites of F protein. Contrarily, SP-A associated with the F(2) subunit, which was highly glycosylated. SP-A but not LF failed to interact with deglycosylated F protein. Moreover, SP-A initiated the hemolyzing fusion activity of F protein. These results suggest that SP-A and LF modulate RSV infection by different binding specificity to F protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Hemolysis
  • Humans
  • Interleukin-8 / biosynthesis
  • Lactoferrin / metabolism*
  • Pulmonary Surfactant-Associated Protein A / metabolism*
  • Respiratory Syncytial Virus Infections / immunology*
  • Viral Proteins / metabolism*

Substances

  • Interleukin-8
  • Pulmonary Surfactant-Associated Protein A
  • Viral Proteins
  • Lactoferrin