2. Academic Validation
  3. 3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a Selective Antagonist of Sphingosine-1-phospahte Receptor Subtype 1, Enhances AMD3100-stimulated Mobilization of Hematopoietic Stem Progenitor Cells in Animals

3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a Selective Antagonist of Sphingosine-1-phospahte Receptor Subtype 1, Enhances AMD3100-stimulated Mobilization of Hematopoietic Stem Progenitor Cells in Animals

  • J Biochem Pharmacol Res. 2013 Dec;1(4):197-203.
Jingjing Liu 1,  Jiawei Zhao 1,  Jen-Fu Lee 1,  Allison Gartung 1,  Hiba Jawadi 1,  Wenliang Zhang 1,  David Lominadze 2,  Menq-Jer Lee 3
Affiliations

Affiliations

  • 1 Bioactive Lipid Research Program, Wayne State University School of Medicine, 540 E. Canfield Avenue, Scott Hall room 9215, Detroit, Michigan 48202 ; Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Scott Hall room 9215, Detroit, Michigan 48202.
  • 2 Department of Physiology and Biophysics, University of Louisville School of Medicine, HSC A-1115, 500 South Preston Street, Louisville, KY 40202.
  • 3 Bioactive Lipid Research Program, Wayne State University School of Medicine, 540 E. Canfield Avenue, Scott Hall room 9215, Detroit, Michigan 48202 ; Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Scott Hall room 9215, Detroit, Michigan 48202 ; Cardiovascular Research Institute, Wayne State University School of Medicine, 540 E. Canfield Avenue, Scott Hall room 9215, Detroit, Michigan 48202 ; Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 540 E. Canfield Avenue, Scott Hall room 9215, Detroit, Michigan 48202.
PMID: 25383272
Abstract

Sphingosine-1-phosphate (S1P), a serum-borne bioactive lipid, regulates various physiological functions. We observed that the S1P receptor subtype 1 (S1P1), a high affinity G-protein coupled receptor of S1P, is the major S1P receptor expressed in the Kit+/Sca-1+/Lin- (KSL) hematopoietic stem progenitor cells (HSPCs, KSL-HSPCs). In this study, we investigate function of S1P1 receptors in the regulation of HSPC mobilization in Animals. Treatment with SEW2871, a specific agonist of S1P1, had no effect on KSL-HSPC mobilization. In addition, mice pretreated with SEW2871 followed by AMD3100, a well-known activator of KSL-HSPC mobilization by antagonizing the stromal-derived factor-1 (SDF-1)/C-X-C Chemokine Receptor type 4 (CXCR4) signaling axis, did not enhance the AMD3100-induced KSL-HSPC mobilization. In contrast, pretreatment of (R)-3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a selective antagonist of S1P1, significantly augments AMD3100-induced KSL-HSPC mobilization into peripheral blood. The inactive enantiomer W140 was incapable of enhancing the AMD3100-induced KSL-HSPC mobilization. Moreover, treatment with selective antagonists for S1P2 and S1P3 had no effects on AMD3100-mediated KSL-HSPC mobilization. Collectively, our data suggest that S1P/S1P1 signaling regulates the SDF-1/CXCR4-mediated retention of KSL-HSPCs in bone marrow microenvironment.

Keywords

CXCR4; SDF-1; W146; hematopoietic stem cells; sphingosine-1-phosphate; sphingosine-1-phosphate receptor.

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