Mast cell carboxypeptidase A, a secretory granule component

摘要: Mast cells are highly granulated of the immune system that upon stimulation release a number inflammatory mediators including heparin and/or chondroitin sulphate (CS) proteoglycan (PG) and various heparin-binding proteases such as tryptase, chymase carboxypeptidase A (CPA). cell CPA is zinc-metalloexopeptidase, cleaving substrates with carboxyl-terminal aliphatic or aromatic amino acids. In this thesis, storage activation was investigated, using bone marrow derived mast (BMMCs) from mice lacking heparin, either due to loss gene coding for biosynthesis enzyme, NDST-2, PG core protein serglycin (SG). We found BMMCs NDST-2-/- thus lack but produce CS, chymase, mMCP-5 mature CPA. Interestingly, pro-form, not active form could be detected in heparin-deficient cells, indicating role processing Furthermore, we have shown cysteine proteases, cathepsins C S, involved CPA, rather cathepsin S cause increased levels well mMCP-5. addition, neither B nor L influence at all, instead, an aspartic protease, E, plays pro-CPA. Further, these studies led novel finding E located inside granules, where it stored complex heparin. The which ultimately leads degranulation, has been studied detail; however, process granules formed gained much attention. addressed issue by use SG. Here, present evidence secretory independently SG mediates selective condensation certain granule constituents, while others independent correctly sorted into subsequently degraded, exocytosed remain unprocessed when absent. These results indicate model selected constituents SG-mediated retention.