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The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor.
Exp Hematol. 2005 Mar; 33(3):295-307.EH

Abstract

OBJECTIVE

Mobilization of hematopoietic stem and progenitor cells (HSPC) by stromal cell-derived factor-1 (SDF-1) has been described; however, sustained adenoviral delivery or N-terminal modification was required for effect and could not be demonstrated with native protein. The aim of this study was to further investigate the SDF-1alpha/CXCR4 axis in HSPC mobilization using CTCE-0021, a cyclized CXCR4 agonist peptide, with comparable bioactivity and improved stability relative to SDF-1alpha.

METHODS

Peripheral blood cells and hematopoietic progenitor cells (HPC) were quantitated in mice administered single or multiple doses of CTCE-0021 or SDF-1alpha, or mobilized by granulocyte colony-stimulating factor (G-CSF) in combination with CTCE-0021. Proteases, cytokines, and receptors implicated in HSPC mobilization were evaluated to determine mechanism of action.

RESULTS

CTCE-0021 dose-dependently elevated blood neutrophils polymorphonuclear neutrophil [PMN] within 5 minutes that peaked after 1 hour and persisted for 24 hours. PMN mobilization could be maintained by daily dosing. CTCE-0021 mobilized colony-forming unit granulocyte macrophage (CFU-GM), burst-forming unit erythroid (BFU-E), and CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM) that peaked within 1 hour after administration, and synergistically enhanced both PMN and HSPC mobilization when combined with G-CSF. Mobilization induced by CTCE-0021 was associated with rapid downregulation of CXCR4 expression on HPC. No appreciable changes in proteases implicated in HPC mobilization were observed. Significantly elevated plasma SDF-1 was detected in mobilized mice, which likely represents CTCE-0021.

CONCLUSION

These studies indicate that CTCE-0021 is an efficient and rapid mobilizer of PMN and HPC when used alone and shows synergistic activity when used in combination with G-CSF. The mobilizing effect of this peptide appears to be mediated by downregulation of the CXCR4 receptor on HPC and altered chemokine gradient.

Authors+Show Affiliations

Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, IN 46202, USA. lpelus@iupui.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15730853

Citation

Pelus, Louis M., et al. "The CXCR4 Agonist Peptide, CTCE-0021, Rapidly Mobilizes Polymorphonuclear Neutrophils and Hematopoietic Progenitor Cells Into Peripheral Blood and Synergizes With Granulocyte Colony-stimulating Factor." Experimental Hematology, vol. 33, no. 3, 2005, pp. 295-307.
Pelus LM, Bian H, Fukuda S, et al. The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. Exp Hematol. 2005;33(3):295-307.
Pelus, L. M., Bian, H., Fukuda, S., Wong, D., Merzouk, A., & Salari, H. (2005). The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. Experimental Hematology, 33(3), 295-307.
Pelus LM, et al. The CXCR4 Agonist Peptide, CTCE-0021, Rapidly Mobilizes Polymorphonuclear Neutrophils and Hematopoietic Progenitor Cells Into Peripheral Blood and Synergizes With Granulocyte Colony-stimulating Factor. Exp Hematol. 2005;33(3):295-307. PubMed PMID: 15730853.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. AU - Pelus,Louis M, AU - Bian,Huimin, AU - Fukuda,Seiji, AU - Wong,Donald, AU - Merzouk,Ahmed, AU - Salari,Hassan, PY - 2004/10/21/received PY - 2004/11/09/revised PY - 2004/11/09/accepted PY - 2005/2/26/pubmed PY - 2005/5/12/medline PY - 2005/2/26/entrez SP - 295 EP - 307 JF - Experimental hematology JO - Exp Hematol VL - 33 IS - 3 N2 - OBJECTIVE: Mobilization of hematopoietic stem and progenitor cells (HSPC) by stromal cell-derived factor-1 (SDF-1) has been described; however, sustained adenoviral delivery or N-terminal modification was required for effect and could not be demonstrated with native protein. The aim of this study was to further investigate the SDF-1alpha/CXCR4 axis in HSPC mobilization using CTCE-0021, a cyclized CXCR4 agonist peptide, with comparable bioactivity and improved stability relative to SDF-1alpha. METHODS: Peripheral blood cells and hematopoietic progenitor cells (HPC) were quantitated in mice administered single or multiple doses of CTCE-0021 or SDF-1alpha, or mobilized by granulocyte colony-stimulating factor (G-CSF) in combination with CTCE-0021. Proteases, cytokines, and receptors implicated in HSPC mobilization were evaluated to determine mechanism of action. RESULTS: CTCE-0021 dose-dependently elevated blood neutrophils polymorphonuclear neutrophil [PMN] within 5 minutes that peaked after 1 hour and persisted for 24 hours. PMN mobilization could be maintained by daily dosing. CTCE-0021 mobilized colony-forming unit granulocyte macrophage (CFU-GM), burst-forming unit erythroid (BFU-E), and CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM) that peaked within 1 hour after administration, and synergistically enhanced both PMN and HSPC mobilization when combined with G-CSF. Mobilization induced by CTCE-0021 was associated with rapid downregulation of CXCR4 expression on HPC. No appreciable changes in proteases implicated in HPC mobilization were observed. Significantly elevated plasma SDF-1 was detected in mobilized mice, which likely represents CTCE-0021. CONCLUSION: These studies indicate that CTCE-0021 is an efficient and rapid mobilizer of PMN and HPC when used alone and shows synergistic activity when used in combination with G-CSF. The mobilizing effect of this peptide appears to be mediated by downregulation of the CXCR4 receptor on HPC and altered chemokine gradient. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/15730853/The_CXCR4_agonist_peptide_CTCE_0021_rapidly_mobilizes_polymorphonuclear_neutrophils_and_hematopoietic_progenitor_cells_into_peripheral_blood_and_synergizes_with_granulocyte_colony_stimulating_factor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-472X(04)00410-2 DB - PRIME DP - Unbound Medicine ER -