Mcpt4, also known as mouse mast cell protease 4, is a chymase ortholog of human mast cell chymase. It plays crucial roles in various biological processes related to the immune response, tissue integrity, and disease progression. It is involved in pathways such as those regulating the immune response to pathogens, maintaining epithelial barrier integrity, and influencing vascular permeability. Genetic models, especially knockout mouse models, have been instrumental in studying its functions [1-10].

In malaria-induced bacteremia, Mcpt4 -/- mice had lower parasitemia but increased intestinal permeability, earlier ileal MC accumulation, and higher IgE levels. The host response in Mcpt4 -/- mice skewed towards a type-1 immune response, while Mcpt4+/+ mice had a type-2 response. Mcpt4 also impacts parasite transmissibility [1]. In partial unilateral ureteral obstruction, Mcpt4 -/- mice showed less fibrosis development and lower αSMA expression compared to wild-type mice, indicating its role in epithelial-mesenchymal transition and parenchyma lesions [2]. In acute ischemic kidney injury, Mcpt4 -/- mice had worsened kidney function, more neutrophil infiltration, and increased expression of adhesion molecules, suggesting MCPT4 chymase has an anti-inflammatory function in this context [3]. In myocardial infarction, Mcpt4 -/- mice had smaller infarct size, improved cardiac functions, and reduced macrophage content but increased T-cell accumulation [4]. In abdominal aortic aneurysm formation, Mcpt4 -/- mice had reduced AAA formation, fewer inflammatory cells, and less apoptosis, angiogenesis, and elastin fragmentation [5]. In group B Streptococcus infections, MCPT4 -/- mice had increased GBS systemic infection and preterm births, and MCPT4-mediated proteolysis of fibronectin was related to its protective effect [6].

In conclusion, Mcpt4 is essential in modulating immune responses, maintaining tissue integrity, and influencing disease progression in multiple disease areas including malaria, kidney-related diseases, cardiovascular diseases, and bacterial infections. The use of Mcpt4 KO mouse models has significantly advanced our understanding of its functions in these biological processes and disease conditions [1-10].

References:

1. Céspedes, Nora, Donnelly, Erinn L, Lowder, Casey, Van de Water, Judy, Luckhart, Shirley. 2022. Mast Cell Chymase/Mcpt4 Suppresses the Host Immune Response to Plasmodium yoelii, Limits Malaria-Associated Disruption of Intestinal Barrier Integrity and Reduces Parasite Transmission to Anopheles stephensi. In Frontiers in immunology, 13, 801120. doi:10.3389/fimmu.2022.801120. https://pubmed.ncbi.nlm.nih.gov/35154114/

2. Pons, Maguelonne, Ali, Liza, Beghdadi, Walid, El Ghoneimi, Alaa, Blank, Ulrich. 2017. Mast Cells and MCPT4 Chymase Promote Renal Impairment after Partial Ureteral Obstruction. In Frontiers in immunology, 8, 450. doi:10.3389/fimmu.2017.00450. https://pubmed.ncbi.nlm.nih.gov/28523000/

3. Madjene, Lydia Celia, Danelli, Luca, Dahdah, Albert, Perianin, Axel, Blank, Ulrich. 2019. Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment. In Kidney international, 97, 516-527. doi:10.1016/j.kint.2019.08.037. https://pubmed.ncbi.nlm.nih.gov/31866111/

4. Wang, Yunzhe, Liu, Cong-Lin, Fang, Wenqian, Shi, Guo-Ping, Zhang, Jinying. 2019. Deficiency of mouse mast cell protease 4 mitigates cardiac dysfunctions in mice after myocardium infarction. In Biochimica et biophysica acta. Molecular basis of disease, 1865, 1170-1181. doi:10.1016/j.bbadis.2019.01.011. https://pubmed.ncbi.nlm.nih.gov/30639224/

5. Sun, Jiusong, Zhang, Jie, Lindholt, Jes S, Libby, Peter, Shi, Guo-Ping. 2009. Critical role of mast cell chymase in mouse abdominal aortic aneurysm formation. In Circulation, 120, 973-82. doi:10.1161/CIRCULATIONAHA.109.849679. https://pubmed.ncbi.nlm.nih.gov/19720934/

6. Gendrin, Claire, Shubin, Nicholas J, Boldenow, Erica, Rajagopal, Lakshmi, Piliponsky, Adrian M. 2017. Mast cell chymase decreases the severity of group B Streptococcus infections. In The Journal of allergy and clinical immunology, 142, 120-129.e6. doi:10.1016/j.jaci.2017.07.042. https://pubmed.ncbi.nlm.nih.gov/28916188/