CXCR4 engagement is required for HIV-1–induced L-selectin shedding
From the Division of Rheumatology, The Children's Hospital of Philadelphia, Philadelphia, PA; the Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA; and the Department of Immunology, National Jewish Medical and Research Center, Denver, CO.8xm, http://www.100md.com
The chemokine receptor, CXCR4, serves as the primary coreceptor for entry of T-cell tropic human immunodeficiency virus (HIV). Binding of either the CXC-chemokine, stromal-derived factor 1{alpha} (SDF-1{alpha} ), or a CXCR4 antagonist, AMD3100, to CXCR4 inhibits infection of CD4+ T cells by T-tropic HIV-1, although only SDF-1{alpha} triggers T-cell signaling cascades. We have previously demonstrated that ligation of CD4 by T-cell tropic HIV-1 NL4-3 induces metalloproteinase-dependent L-selectin (CD62L) shedding on resting CD4+ T cells. However, the role of CXCR4 in HIV-induced L-selectin shedding is unclear. Here, we show that L-selectin shedding induced by HIV-1 NL4-3 is completely reversed by AMD3100, but not SDF-1{alpha} , although SDF-1{alpha} alone does not induce L-selectin shedding. These results indicate that engagement of both CD4 and CXCR4 is required for HIV-induced shedding of L-selectin on primary resting CD4+ T cells.(JiangFang Wang Susanne Marschner and Terri H. Finkel)
The chemokine receptor, CXCR4, serves as the primary coreceptor for entry of T-cell tropic human immunodeficiency virus (HIV). Binding of either the CXC-chemokine, stromal-derived factor 1{alpha} (SDF-1{alpha} ), or a CXCR4 antagonist, AMD3100, to CXCR4 inhibits infection of CD4+ T cells by T-tropic HIV-1, although only SDF-1{alpha} triggers T-cell signaling cascades. We have previously demonstrated that ligation of CD4 by T-cell tropic HIV-1 NL4-3 induces metalloproteinase-dependent L-selectin (CD62L) shedding on resting CD4+ T cells. However, the role of CXCR4 in HIV-induced L-selectin shedding is unclear. Here, we show that L-selectin shedding induced by HIV-1 NL4-3 is completely reversed by AMD3100, but not SDF-1{alpha} , although SDF-1{alpha} alone does not induce L-selectin shedding. These results indicate that engagement of both CD4 and CXCR4 is required for HIV-induced shedding of L-selectin on primary resting CD4+ T cells.(JiangFang Wang Susanne Marschner and Terri H. Finkel)