Published online before print July 22, 2003
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* Experimental Transplantation and Immunology Branch and
HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and
Division of Biostatistics, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Rockville, Maryland
1Correspondence: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 12N226, MSC 1907, Bethesda, MD 20892. E-mail: tosatog{at}mail.nih.gov
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.
Key Words: chemokine • cytokine • chemokine processing • AIDS • anti-HIV therapy
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