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(Journal of Leukocyte Biology. 2001;70:431-438.)
© 2001 by Society for Leukocyte Biology

CXCR4 undergoes complex lineage and inducing agent-dependent dissociation of expression and functional responsiveness to SDF-1 during myeloid differentiation

Department of Cardiovascular Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania

Correspondence: Dr. Shalley K. Gupta, Department of CV Biology, Mail Code UW2511, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406. E-mail: Shalley_K_Gupta{at}sbphrd.com

The CXC chemokine SDF-1 and its receptor CXCR4 mediate myelopoiesis, presumably by regulating the homing of hematopoietic progenitor cells. We used the inducible HL-60 cell line as a model system for comparative analysis of CXCR4 expression during differential maturation into the granulocytic or monocytic phenotypes. Five different measures of CXCR4 expression and functional coupling: mRNA and surface expression, SDF-1-mediated [³⁵S]GTPS binding, calcium flux, and chemotaxis were examined simultaneously. Granulocytic differentiation with dimethyl sulfoxide induced surface expression of CXCR4 as well as SDF-1-mediated [³⁵S]GTPS binding and chemotaxis, whereas calcium flux was attenuated by twofold to threefold in HL-60 cells. Conversely, monocytic differentiation with vitamin D₃ inhibited surface expression and SDF-1-mediated chemotaxis, even as it induced [³⁵S]GTPS binding and calcium flux by more than twofold. Sodium butyrate up-regulated all parameters of CXCR4 expression studied. Together, these results demonstrate that CXCR4 expression undergoes complex regulation at multiple checkpoints, with the likely involvement of different G-proteins for signal transduction during cellular differentiation and following activation with SDF-1.

Key Words: chemokines • cellular differentiation • granulocytes • monocytes

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