title: Mast cell cathepsins C and S control levels of carboxypeptidase A and the chymase, mouse mast cell protease 5.
abstract: Carboxypeptidase A (CPA) is a metalloprotease, residing in the mast cell secretory granules together with chymases and tryptases. Little information is available with respect to the mechanisms that maintain or regulate the levels of stored proteases in the mast cell secretory granules. In this study we examined whether cathepsins C and S may be involved in the control of the levels of mast cell proteases. Mast cells cultured from bone marrow of cathepsin C- or S-null mice expressed higher levels of CPA protein and activity than cells from wild-type mice. Similar increases in protein were observed for the mouse chymase, mast cell protease-5 (mMCP-5), but not for the tryptase, mMCP-6. Steady-state levels of CPA and mMCP-5 mRNA were similar in wild-type and cathepsin C-null mast cells, indicating that post-transcriptional mechanisms explain the observed cathepsin C-dependence of CPA and mMCP-5 expression. The present study thus indicates novel roles for cathepsins C and S in regulating the levels of stored proteases in the mast cell secretory granules.
authors.affiliation: Swedish University of Agricultural Sciences, Department of Veterinary Medical Chemistry, The Biomedical Center, Box 575, S-751 23 Uppsala, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Henningsson
authors.forename: Paul
authors.initials: P
authors.lastname: Wolters
authors.forename: Harold A
authors.initials: HA
authors.lastname: Chapman
authors.forename: George H
authors.initials: GH
authors.lastname: Caughey
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology; D043422:Carboxypeptidases A / Q000096:biosynthesis / Q000378:metabolism*; D020789:Cathepsin C / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002403:Cathepsins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D053818:Chymases; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D023421:Models, Animal; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D022142:Secretory Vesicles / Q000201:enzymology; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D053802:Tryptases
chemical_list: D000199:Actins; D012333:RNA, Messenger; C509190:Tpsb2 protein, mouse; D002403:Cathepsins; D020789:Cathepsin C; D043422:Carboxypeptidases A; D012697:Serine Endopeptidases; D053818:Chymases; C509222:Tpsab1 protein, mouse; D053802:Tryptases; C028217:cathepsin S