The Journal of Experimental Medicine
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Published 4 August 2003. doi:10.1084/jem.20030671
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© Rockefeller University Press, 0022-1007/2003/8/423 $5.00
The Journal of Experimental Medicine, Volume 198, Number 3, 423-431

The Chymase, Mouse Mast Cell Protease 4, Constitutes the Major Chymotrypsin-like Activity in Peritoneum and Ear Tissue. A Role for Mouse Mast Cell Protease 4 in Thrombin Regulation and Fibronectin Turnover

Elena Tchougounova, Gunnar Pejler and Magnus Åbrink

Swedish University of Agricultural Sciences, Department of Molecular Biosciences, The Biomedical Center, Box 575, 751 23 Uppsala, Sweden

Address correspondence to Magnus Åbrink, Swedish University of Agricultural Sciences, Department of Molecular Biosciences, The Biomedical Center, Box 575, 751 23 Uppsala, Sweden. Phone: 46-18-4714192; Fax: 46-18-550762; email: magnus.abrink{at}bmc.uu.se

To gain insight into the biological role of mast cell chymase we have generated a mouse strain with a targeted deletion in the gene for mast cell protease 4 (mMCP-4), the mouse chymase that has the closest relationship to the human chymase in terms of tissue localization and functional properties. The inactivation of mMCP-4 did not affect the storage of other mast cell proteases and did not affect the number of mast cells or the mast cell morphology. However, mMCP-4 inactivation resulted in complete loss of chymotryptic activity in the peritoneum and in ear tissue, indicating that mMCP-4 is the main source of stored chymotrypsin-like protease activity at these sites. The mMCP-4 null cells showed markedly impaired ability to perform inactivating cleavages of thrombin, indicating a role for mMCP-4 in regulating the extravascular coagulation system. Further, a role for mMCP-4 in connective tissue remodeling was suggested by the inability of mMCP-4 null peritoneal cells to process endogenous fibronectin.

Key Words: chymase • mast cell • fibronectin • thrombin • mouse mast cell protease 4


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