Biology:CXCL2

From HandWiki
Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example
chemokine (C-X-C motif) ligand 2
Identifiers
SymbolCXCL2
Alt. symbolsSCYB2, GRO2, GROb, MIP-2a, MGSA-b, CINC-2a
NCBI gene2920
HGNC4603
OMIM139110
RefSeqNM_002089
UniProtP19875
Other data
LocusChr. 4 q21

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.[1][2][3] The gene for CXCL2 is located on human chromosome 4 in a cluster of other CXC chemokines.[4] CXCL2 mobilizes cells by interacting with a cell surface chemokine receptor called CXCR2.[3]

CXCL2, like related chemokines, is also a powerful neutrophil chemoattractant and is involved in many immune responses including wound healing, cancer metastasis, and angiogenesis.[5] 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.[5]

Clinical development

CXCL2 in combination with the CXCR4 inhibitor plerixafor rapidly mobilizes hematopoietic stem cells into the peripheral blood.[6]

This rapid peripheral blood stem cell mobilization regimen entered Phase 2 clinical trials in 2021[7][8] in development by Magenta Therapeutics[9] as a new method to collect stem cells for bone marrow transplantation.

References

  1. "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. January 1989. doi:10.1073/pnas.86.2.612. PMID 2643119. Bibcode1989PNAS...86..612W. 
  2. "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. October 1990. doi:10.1128/mcb.10.10.5596. PMID 2078213. 
  3. 3.0 3.1 "Peripheral blood stem cell mobilization: the CXCR2 ligand GRObeta rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties". Experimental Hematology 34 (8): 1010–20. August 2006. doi:10.1016/j.exphem.2006.04.004. PMID 16863907. 
  4. "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenetics and Cell Genetics 84 (1–2): 39–42. 1999. doi:10.1159/000015209. PMID 10343098. 
  5. 5.0 5.1 "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. September 2013. doi:10.4049/jimmunol.1203421. PMID 23904157. 
  6. "Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell". Cell 172 (1–2): 191–204.e10. January 2018. doi:10.1016/j.cell.2017.11.003. PMID 29224778. PMC 5812290. https://doi.org/10.1016/j.cell.2017.11.003. 
  7. 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
  8. 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
  9. "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" (in en). https://investor.magentatx.com/news-releases/news-release-details/magenta-therapeutics-announces-additional-preliminary-positive/.