CXCL2

CXCL2

CXCL2

Mammalian protein found in Homo sapiens

Chemokine (C-X-C motif) ligand 2 (CXCL2) is a small cytokine belonging to the CXC chemokine family that is also called macrophage inflammatory protein 2-alpha (MIP2-alpha), Growth-regulated protein beta (Gro-beta) and Gro oncogene-2 (Gro-2). CXCL2 is 90% identical in amino acid sequence as a related chemokine, CXCL1. This chemokine is secreted by monocytes and macrophages and is chemotactic for polymorphonuclear leukocytes and hematopoietic stem cells.[5][6][7] The gene for CXCL2 is located on human chromosome 4 in a cluster of other CXC chemokines.[8] CXCL2 mobilizes cells by interacting with a cell surface chemokine receptor called CXCR2.[7]

Quick Facts Available structures, PDB ...
Quick Facts chemokine (C-X-C motif) ligand 2, Identifiers ...

CXCL2, like related chemokines, is also a powerful neutrophil chemoattractant and is involved in many immune responses including wound healing, cancer metastasis, and angiogenesis.[9] A study was published in 2013 testing the role of CXCL2, CXCL3, and CXCL1 in the migration of airway smooth muscle cells (ASMCs) migration which plays a significant role in asthma. The results of this study showed that CXCL2 and CXCL3 both help with the mediation of normal and asthmatic ASMC migration through different mechanisms.[9]

Clinical development

CXCL2 in combination with the CXCR4 inhibitor plerixafor rapidly mobilizes hematopoietic stem cells into the peripheral blood.[10]

This rapid peripheral blood stem cell mobilization regimen entered Phase 2 clinical trials in 2021[11][12] in development by Magenta Therapeutics[13] as a new method to collect stem cells for bone marrow transplantation.

References

  1. [1]
    GRCh38: Ensembl release 89: ENSG00000081041 – Ensembl, May 2017
  2. [2]
    GRCm38: Ensembl release 89: ENSMUSG00000029380 – Ensembl, May 2017
  3. [3]
    "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. [4]
    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. [5]
    Wolpe SD, Sherry B, Juers D, Davatelis G, Yurt RW, Cerami A (January 1989). "Identification and characterization of macrophage inflammatory protein 2". Proceedings of the National Academy of Sciences of the United States of America. 86 (2): 612–6. Bibcode:1989PNAS...86..612W. doi:10.1073/pnas.86.2.612. PMC 286522. PMID 2643119.
  6. [6]
    Iida N, Grotendorst GR (October 1990). "Cloning and sequencing of a new gro transcript from activated human monocytes: expression in leukocytes and wound tissue". Molecular and Cellular Biology. 10 (10): 5596–9. doi:10.1128/mcb.10.10.5596. PMC 361282. PMID 2078213.
  7. [7]
    Pelus LM, Fukuda S (August 2006). "Peripheral blood stem cell mobilization: the CXCR2 ligand GRObeta rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties". Experimental Hematology. 34 (8): 1010–20. doi:10.1016/j.exphem.2006.04.004. PMID 16863907.
  8. [8]
    O'Donovan N, Galvin M, Morgan JG (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenetics and Cell Genetics. 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098. S2CID 8087808.
  9. [9]
    Al-Alwan LA, Chang Y, Mogas A, Halayko AJ, Baglole CJ, Martin JG, et al. (September 2013). "Differential roles of CXCL2 and CXCL3 and their receptors in regulating normal and asthmatic airway smooth muscle cell migration". Journal of Immunology. 191 (5): 2731–41. doi:10.4049/jimmunol.1203421. PMC 3748335. PMID 23904157.
  10. [10]
    Hoggatt J, Singh P, Tate TA, Chou BK, Datari SR, Fukuda S, et al. (January 2018). "Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell". Cell. 172 (1–2): 191–204.e10. doi:10.1016/j.cell.2017.11.003. PMC 5812290. PMID 29224778.
  11. [11]
    Clinical trial number NCT04762875 for "A Phase II Study Evaluating the Safety and Efficacy of MGTA-145 in Combination With Plerixafor for the Mobilization and Transplantation of HLA-Matched Donor Hematopoietic Stem Cells in Recipients With Hematological Malignancies" at ClinicalTrials.gov
  12. [12]
    Clinical trial number NCT04552743 for "Phase II Study of MGTA-145 in Combination With Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Patients With Multiple Myeloma" at ClinicalTrials.gov
  13. [13]
    "Magenta Therapeutics Announces Additional Preliminary Positive Results from Ongoing Phase 2 Clinical Trial of MGTA-145 and Plerixafor in Patients with Multiple Myeloma at the American Society of Clinical Oncology (ASCO) Annual Meeting – Magenta Therapeutics". investor.magentatx.com. Retrieved 2021-10-22.
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