Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection.

Abstract

The distribution of secretory leukocyte protease inhibitor (SLPI) at entry portals indicates its involvement in defending the host from pathogens, consistent with the ability of SLPI to inhibit human immunodeficiency virus (HIV)-1 infection by an unknown mechanism. We now demonstrate that SLPI binds to the membrane of human macrophages through the phospholipid-binding protein, annexin II. Based on the recent identification of human cell membrane phosphatidylserine (PS) in the outer coat of HIV-1, we define a novel role for annexin II, a PS-binding moiety, as a cellular cofactor supporting macrophage HIV-1 infection. Moreover, this HIV-1 PS interaction with annexin II can be disrupted by SLPI or other annexin II-specific inhibitors. The PS-annexin II connection may represent a new target to prevent HIV-1 infection.

• Authors: Ge Ma, Teresa Greenwell-Wild, Kejian Lei, Wenwen Jin, Jennifer Swisher, Neil Hardegen, Carl T Wild, Sharon M Wahl
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 200 Issue 10 Pg. 1337-46 (Nov 15 2004) ISSN: 0022-1007 [Print] United States
• PMID: 15545357 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Annexin A2
• DNA Primers
• Phosphatidylserines
• Proteinase Inhibitory Proteins, Secretory
• Proteins
• RNA, Small Interfering
• SLPI protein, human
• Secretory Leukocyte Peptidase Inhibitor

Topics

• Annexin A2 (metabolism)
• Blotting, Western
• Cell Line
• Chromatography, High Pressure Liquid
• DNA Primers
• Flow Cytometry
• HIV Infections (metabolism)
• HIV-1 (metabolism)
• Humans
• Immunoprecipitation
• Macrophages (metabolism, virology)
• Mass Spectrometry
• Microscopy, Fluorescence
• Phosphatidylserines (metabolism)
• Proteinase Inhibitory Proteins, Secretory
• Proteins (metabolism)
• RNA, Small Interfering (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Secretory Leukocyte Peptidase Inhibitor