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

Journal of Leukocyte Biology

Richard Little³  Robert Yarchoan³  Yoshiyasu Aoki²  Kathleen Wyvill³  David Davis³  Ombretta Salvucci²  Maria De La Luz Sierra²  Ghanshyam Gupta¹  Giovanna Tosato²  Sabrina Villalba² 

[1] Division of Biostatistics, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Rockville, Maryland Division of Biostatistics, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Rockville, Maryland Division of Biostatistics, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Rockville, Maryland;Experimental Transplantation and Immunology Branch and Experimental Transplantation and Immunology Branch and Experimental Transplantation and Immunology Branch and;HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and

关键词: chemokine;    cytokine;    chemokine processing;    AIDS;    anti-HIV therapy;   

DOI  :  10.1189/jlb.0403149

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown