Biological significance of the expression of HIV-related chemokine coreceptors (CCR5 and CXCR4) and their ligands by human hematopoietic cell lines

Abstract

The aim of this study was to learn more about the role of the HIV-related chemokine-chemokine receptor axes in human hematopoiesis. To address this issue we phenotyped 35 selected hematopoietic cell lines for the expression of CD4, CXCR4 and CCR5. We next evaluated the functionality of these chemokine receptors by calcium flux and chemotaxis assays, and by the ability of SDF-1, MIP-1␣, MIP-1␤ and RANTES to influence the growth of the cells expressing CXCR4 and/or CCR5. Lastly, we examined whether human hematopoietic cell lines may secrete some HIV-related chemokines, and whether endogenously secreted chemokines might interfere with the infectability of hematopoietic cells by X4 and R5 HIV strains. These results demonstrate that: (1) HIV-related receptors are widely expressed on human hematopoietic cell lines; (2) stimulation of CXCR4 by SDF-1 induces calcium flux and chemotaxis in several hematopoietic cell lines more efficiently than stimulation of CCR5 by receptor-specific ␤-chemokines; (3) chemokines do not regulate proliferation of the hematopoietic cells; and finally (4) infectability of the hematopoietic cells by HIV-1 may be auto-modulated by endogenously secreted chemokines. These data shed more light on the role of HIV-related chemokine-chemokine receptors axes in human hematopoiesis and interaction of hematopoietic cells with HIV. Leukemia (2000) 14, 1821-1832.

CXCR4–SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion

“…Generally, the biologic effects of SDF-1 on RMS cells observed here are consistent with those reported by us and others for human hematopoietic cells [6][7][8]22,23 and involve primarily cell interactions with the microenvironment and their migration rather than cell proliferation and/or survival. [6][7][8][9]22,23 However, the possibility that SDF-1 influences the metastatic potential of RMS in synergy/ cooperation with other factors cannot be excluded.…”

“…22 The CXCR4 antigen was detected with phycoerythrin (PE)-anti-CXCR4 monoclonal antibody (MoAb; R&D Systems, Minneapolis, MN), clone no. 12.G5.…”

The SDF‐1‐CXCR4 Axis Stimulates VEGF Secretion and Activates Integrins but does not Affect Proliferation and Survival in Lymphohematopoietic Cells

“…Based on these and our other observations [11,12,19,38], we conclude that SDF-1 is an important factor regulating the interaction of lymphohematopoietic cells with the microenvironment but is not primarily involved in regulating proliferation or survival of these cells.…”

“…Previously we reported that several human hematopoietic cell lines expressed the HIV-related chemokine receptors CXCR4 and CCR5 [19]. In our current study, we selected 26 human CXCR4 (Tables 1-3).…”

Stromal-derived factor 1 inhibits the cycling of very primitive human hematopoietic cells in vitro and in NOD/SCID mice

“…25,56,66 On certain myeloid progenitor cell lines, a suppressive effect of SDF-1 was reported, 67 although this was not the case for others, in spite of expression of functional CXCR4. 68 In combination with other cytokines, SDF-1 was actually found to promote the proliferation of human CD34 ϩ cells purified from normal adult peripheral blood although when SDF-1 was added alone, only survival was supported, not mitogenesis. 69 These findings highlight the role other factors can have in influencing the effects chemokines exert on hematopoietic cell proliferation control as well as the importance of the progenitor subset investigated, as is also indicated by earlier evidence of opposing actions of MIP-1␣ (and TGF-␤) in stimulating the proliferation of later progenitor types but inhibiting their more primitive precursors.…”