Chymase

chymase 1, mast cell
Chymase with PMSF bound PDB: 1KLT
Identifiers
SymbolCMA1
NCBI gene1215
HGNC2097
OMIM118938
RefSeqNM_001836
UniProtP23946
Other data
EC number3.4.21.39
LocusChr. 14 q11.2
Search for
StructuresSwiss-model
DomainsInterPro

Chymases (EC 3.4.21.39) are a group of serine proteases found primarily in mast cells. Humans have a single chymase gene, CMA1, which encodes α-chymase, whereas rodents have several distinct chymase genes. In mice, these include the β-chymase genes Mcpt1, Mcpt2 and Mcpt4, and the α-chymase gene Cma1, also known as Mcpt5. These genes encode distinct proteins rather than alternative splice variants of a single gene. Their expression differs among mast cell populations: mouse mucosal mast cells typically express mMCP-1 and mMCP-2, whereas connective tissue-type mast cells express mMCP-4 and mMCP-5.

A separate mouse protease, mMCP-8, is associated primarily with basophil granulocytes and should not be confused with α-chymase. Derakhshan and colleagues identified transcripts for its gene, Mcpt8, in an inducible lung mast cell population that expands during allergic airway inflammation.

Function

Chymases participate in inflammatory responses and host defense. In mouse studies of intestinal nematode infection, circulating mMCP-1 has been measured as a marker of mucosal mast cell activation. During infection with Trichinella spiralis, mMCP-1 contributes to increased intestinal epithelial permeability. Mast cell responses have also been investigated during infection with Trichuris muris.

Clinical significance

Chymases are known to convert angiotensin I to angiotensin II and thus play a role in hypertension and atherosclerosis.

Because of its role in inflammation it has been investigated as a target in the treatment of asthma.

References

  1. ↑ Pejler G (2020). "Novel Insight into the in vivo Function of Mast Cell Chymase: Lessons from Knockouts and Inhibitors". Journal of Innate Immunity. 12 (5): 357–372. doi:10.1159/000506985. PMC 7506261. PMID 32498069.
  2. ↑ Derakhshan T, Samuchiwal SK, Hallen N, Bankova LG, Boyce JA, Barrett NA, et al. (January 2021). "Lineage-specific regulation of inducible and constitutive mast cells in allergic airway inflammation". The Journal of Experimental Medicine. 218 (1) e20200321. doi:10.1084/jem.20200321. PMC 7953627. PMID 32946563.
  3. ↑ McDermott JR, Bartram RE, Knight PA, Miller HR, Garrod DR, Grencis RK (June 2003). "Mast cells disrupt epithelial barrier function during enteric nematode infection". Proceedings of the National Academy of Sciences of the United States of America. 100 (13): 7761–7766. Bibcode:2003PNAS..100.7761M. doi:10.1073/pnas.1231488100. PMC 164661. PMID 12796512.
  4. ↑ Betts CJ, Else KJ (January 1999). "Mast cells, eosinophils and antibody-mediated cellular cytotoxicity are not critical in resistance to Trichuris muris". Parasite Immunology. 21 (1): 45–52. doi:10.1046/j.1365-3024.1999.00200.x. PMID 10081771. S2CID 31343469.
  5. ↑ Blackwell NM, Else KJ (June 2001). "B cells and antibodies are required for resistance to the parasitic gastrointestinal nematode Trichuris muris". Infection and Immunity. 69 (6): 3860–3868. doi:10.1128/IAI.69.6.3860-3868.2001. PMC 98409. PMID 11349052.
  6. ↑ Caughey GH (June 2007). "Mast cell tryptases and chymases in inflammation and host defense". Immunological Reviews. 217: 141–154. doi:10.1111/j.1600-065X.2007.00509.x. PMC 2275918. PMID 17498057.
  7. ↑ de Garavilla L, Greco MN, Sukumar N, Chen ZW, Pineda AO, Mathews FS, et al. (May 2005). "A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo". The Journal of Biological Chemistry. 280 (18): 18001–18007. doi:10.1074/jbc.M501302200. PMID 15741158.