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Modulation of CXCR4 expression and SDF‐1α functional activity during differentiation of human monocytes and macrophages
Author(s) -
Gupta Shalley K.,
Pillarisetti Kodandaram,
Lysko Paul G.
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.66.1.135
Subject(s) - biology , chemokine , monocyte , cxcr4 , chemokine receptor , microbiology and biotechnology , flow cytometry , stromal cell , macrophage , stimulation , receptor , granulocyte , immunology , endocrinology , inflammation , cancer research , biochemistry , in vitro
Chemoattraction of monocytes by the CXC chemokine stromal cell‐derived factor‐1α (SDF‐1α) and its receptor CXCR4 may be involved in vascular diseases like atherosclerosis. We studied the regulation of CXCR4 transcription and SDF‐1‐induced functional responses in human monocytes during their differentiation in the presence of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), oxidized low‐density lipoprotein (Ox‐LDL), and unmodified LDL. Our results reveal that the rapid decline of SDF‐1‐mediated [Ca 2+ ] i influx after monocyte isolation is followed by a gradual functional restoration and a concomitant re‐expression of CXCR4 mRNA over time. A further three‐ to fourfold induction of CXCR4 mRNA occurred in macrophage‐derived foam cells on treatment with Ox‐LDL. HL‐60 cells induced with phorbol myristate acetate (PMA) showed a rapid fourfold stimulation of CXCR4 mRNA within 1 h, declining to barely detectable levels at 3 h, with eventual restoration over time, mirroring the expression pattern in monocytes. Surface expression of CXCR4 is maintained in HL‐60 cells during PMA‐induced differentiation, as demonstrated by flow cytometry. GM‐CSF had no effect on CXCR4 mRNA in HL‐60 cells and does not cause its down‐regulation in human macrophages. J. Leukoc. Biol. 66: 135–143; 1999.