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.
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.
Tchougounova
Elena
E
Swedish University of Agricultural Sciences, Department of Molecular Biosciences, The Biomedical Center, Box 575, 751 23 Uppsala, Sweden.
Pejler
Gunnar
G
Abrink
Magnus
M
D000818:Animals; D000001:Calcimycin / Q000378:metabolism; D002478:Cells, Cultured; D004423:Ear; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007476:Ionophores / Q000378:metabolism; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D010537:Peritoneum / Q000166:cytology / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D014020:Tissue Extracts / Q000378:metabolism
D007476:Ionophores; D014020:Tissue Extracts; D007073:Immunoglobulin E; D000001:Calcimycin; D012697:Serine Endopeptidases; C066932:mast cell protease 4; D013917:Thrombin