The Journal of Experimental Medicine
Cytokines Montreal 2008
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Published 15 November 2004. doi:10.1084/jem.20041115
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 10, 1337-1346
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Secretory Leukocyte Protease Inhibitor Binds to Annexin II, a Cofactor for Macrophage HIV-1 Infection

Ge Ma1, Teresa Greenwell-Wild1, Kejian Lei1, Wenwen Jin1, Jennifer Swisher1, Neil Hardegen1, Carl T. Wild2, and Sharon M. Wahl1

1 Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD 20892
2 Panacos Pharmaceuticals, Inc., Gaithersburg, MD 20877

Address correspondence to Sharon M. Wahl, Oral Infection and Immunity Branch, NIDCR, NIH, 30 Convent Dr., MSC4352, Building 30, Room 320, Bethesda, MD 20892. Phone: (301) 496-4178; Fax: (301) 402-1064; email: smwahl{at}dir.nidcr.nih.gov

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.

Key Words: retrovirus • monocytes • AIDS • fusion • phosphatidylserine


G. Ma and T. Greenwell-Wild contributed equally to this work.

Abbreviations used in this paper: LC-MS/MS, nano-capillary HPLC ion trap mass spectrometry; PS, phosphatidylserine; rhSLPI, recombinant human secretory leukocyte protease inhibitor; RNAi, RNA-mediated interference; siRNA, small interfering RNA; SLPI, secretory leukocyte protease inhibitor.


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