Serum inactivation contributes to the failure of stromal-derived factor-1 to block HIV-I infection in vivo.

Abstract	The chemokine stromal-derived factor-1 (SDF-1) can block human immunodeficiency virus type 1 (HIV-1) infection in vitro by binding to the CXC chemokine receptor, CXCR-4, which serves as a coreceptor for T cell tropic HIV-1. In spite of being constitutively expressed in vivo, SDF-1 does not appear to block HIV-1 infection and spread in vivo. We report that SDF-1 is consistently measured in normal serum (15.4+/-3.0 ng/ml; mean+/-sd) and in serum from AIDS patients (16.6+/-3.7 ng/ml). However, we find that circulating SDF-1 is modified to an inactive form. When exposed to serum, recombinant SDF-1 is specifically and rapidly altered to yield an apparently smaller chemokine that does not bind to SDF-1 receptor-expressing cells, does not have chemoattractive or pre-B cell stimulatory activity, and does not block HIV-1 infection. Thus, serum modification and inactivation contribute to the failure of SDF-1 to block HIV-1 infection and spread in man. The inactivation of circulating SDF-1 may be critical in permitting local gradients to develop and direct cell trafficking.
Authors	Sabrina Villalba, Ombretta Salvucci, Yoshiyasu Aoki, Maria De La Luz Sierra, Ghanshyam Gupta, David Davis, Kathleen Wyvill, Richard Little, Robert Yarchoan, Giovanna Tosato
Journal	Journal of leukocyte biology (J Leukoc Biol) Vol. 74 Issue 5 Pg. 880-8 (Nov 2003) ISSN: 0741-5400 [Print] United States
PMID	12960279 (Publication Type: Comparative Study, Journal Article)
Chemical References	CXCL12 protein, human Chemokine CXCL12 Chemokines, CXC Cxcl12 protein, mouse Immunoglobulin G Receptors, Interleukin-8A
Topics	Acquired Immunodeficiency Syndrome (blood, prevention & control) Animals Cell Division Cell Line Cells, Cultured Chemokine CXCL12 Chemokines, CXC (blood, immunology, isolation & purification, physiology) Endothelium, Vascular (physiology) Enzyme-Linked Immunosorbent Assay Flow Cytometry HIV-1 Humans Immunoglobulin G Leukocytes, Mononuclear (drug effects, physiology, virology) Mice Receptors, Interleukin-8A (antagonists & inhibitors) Reference Values Stromal Cells (physiology) Umbilical Veins

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