Journal
EXPERIMENTAL HEMATOLOGY
Volume 28, Issue 12, Pages 1334-1342Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0301-472X(00)00541-5
Keywords
CD34(+) cells; chemokines; HIV; CCRS
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Funding
- NHLBI NIH HHS [R01 HL61796-01] Funding Source: Medline
- NIAID NIH HHS [R01 AI-4083] Funding Source: Medline
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Objective. The resistance of human bone marrow (BM) CD34(+) cells to human immunodeficiency virus (HIV) infection is at this point not fully understood. Recently we reported that the chemokines MIP-1 alpha, MIP-1 beta, and RANTES secreted by BM-derived CD34(+) cells may compete with the macrophagotropic HIV (R5 HIV) strain for the CCR5 coreceptor. Materials and Methods. In this study we extended our previous observations and examined various lympho-hematopoietic CD34(+) cells isolated from thymus (Th), cord blood (CB), mobilized peripheral blood (mPB), and BM for the expression of beta -chemokines binding to CCR5, i.e., MTP-1 alpha, MIP-1 beta, RANTES, MCP-2, MCP-3, and MCP-4, and the alpha chemokine SDF-1 (binding to CXCR4) as these chemokines may compete with the R5 and X4 HIV strains, respectively, far entry into cells. Results. We found that Th-, CB-, mPB-, and BM-derived CD34(+) cells express mRNA transcripts for all the beta -chemokines tested but not for SDF-1. Using sensitive ELISA assays we found that although MIP-1 alpha and MIP-1 beta proteins were secreted by all the lympho-hematopoietic CD34(+) cells tested, RANTES was detectable only in media conditioned by BM- and CB-derived CD34(+) cells and not Th-derived cells. However, media conditioned by BM-, mPB- and Th-derived CD34(+) cells protected the T lymphocytic cell line (PB-1) from infection by the RS but not the X4 HIV strain. Conclusions. Hence this study demonstrates that beta -chemokines are secreted by lymphohematopoietic CD34(+) cells originating from various sources and that these endogenously secreted chemokines may limit entry of the R5 HN strain into the cells by competing for the CCR5 coreceptor. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.
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