- Title
- Experimental arthritis is dependent on mouse mast cell protease-5
- Creator
- Stevens, Richard L.; McNeil, H. Patrick; Wensing, Lislaine A.; Shin, Kichul; Wong, G. William; Hansbro, Philip M.; Krilis, Steven A.
- Relation
- Journal of Biological Chemistry Vol. 292, Issue 13, p. 5392-5404
- Publisher Link
- http://dx.doi.org/10.1074/jbc.M116.773416
- Publisher
- American Society for Biochemistry and Molecular Biology
- Resource Type
- journal article
- Date
- 2017
- Description
- The constitutive heparin⁺ (HP) mast cells (MCs) in mice express mouseMCprotease (mMCP)-5 and carboxypeptidaseA (mMC-CPA). The amino acid sequence ofmMCP-5is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2⁺ MCs in the jejunal mucosa of Trichinella spiralis-infected mice. In contrast, the constitutive HP⁺ MCs in the tongues of mMCP-5-null mice were poorly granulated and lacked mMC-CPA protein. Bone marrow-derived MCs were readily developed from the transgenic mice using IL-3. Although these MCs contained high levels of mMC-CPA mRNA, they also lacked the latter exopeptidase. mMCP-5 protein is therefore needed to target translated mMC-CPA to the secretory granule along with HP-containing serglycin proteoglycans. Alternately, mMCP-5 is needed to protect mMC-CPA from autolysis in the cell's granules. Fibronectin was identified as a target of mMCP-5, and the exocytosis ofmMCP-5from theMCs in the mouse's peritoneal cavity resulted in the expression of metalloproteinase protease-9, which has been implicated in arthritis. In support of the latter finding, experimental arthritis was markedly reduced in mMCP-5-null mice relative to wildtype mice in two disease models.
- Subject
- arthritis; heparin⁺ mast cells; mast cells; heparin⁺
- Identifier
- http://hdl.handle.net/1959.13/1399806
- Identifier
- uon:34679
- Identifier
- ISSN:0021-9258
- Rights
- This research was originally published in the Journal of Biological Chemistry. © 2017. The Author(s).
- Language
- eng
- Full Text
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