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

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.

• Authors: Hitomi Sano, Kazushige Nagai, Hiroyuki Tsutsumi, Yoshio Kuroki
• Journal: European journal of immunology (Eur J Immunol) Vol. 33 Issue 10 Pg. 2894-902 (Oct 2003) ISSN: 0014-2980 [Print] Germany
• PMID: 14515273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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