title: Secretory apparatus assessed by analysis of pancreatic secretory stress protein expression in a rat model of chronic pancreatitis.
abstract: Secretory stress proteins (SSP) are a family of proteins including isoforms of pancreatitis-associated protein (PAP) and pancreatic stone protein (PSP/reg). In vitro exposure to trypsin results in the formation of insoluble fibrillar structures. SSP are constitutively secreted into pancreatic juice at low levels. The WBN/Kob rat is a model for chronic pancreatitis, displaying focal inflammation, destruction of the parenchyma and changes in the architecture of the acinar cell; the synthesis and secretion of SSP are also increased. We have investigated the secretory apparatus by SSP immunohistochemistry at the light- and electron-microscopical (EM) levels. Immunocytochemistry of PSP/reg in Wistar control rats reveals low levels, with individual acinar cells exhibiting high immunoreactivity in zymogen granules. PAP is not detectable. In the WBN/Kob rat, PSP/reg and PAP immunoreactivity is markedly increased. Double immunofluorescence for PSP/reg and PAP I or II demonstrates that these proteins colocalize to the same cell. Acinar cells change their secretory architecture by fusion of zymogen granules and elongation of the fused organelles. The immunogold technique has demonstrated an increase of SSP in zymogen granules in WBN/Kob rats. PSP/reg-positive zymogen granules fuse to form elongated structures with fibrillar contents. An extensive PSP/reg-positive fibrillar network is established in the cytosol. Extracellular fibrils have been observed in several ductules. Thus, SSP-derived fibrils form concomitantly with acinar damage in the WBN/Kob rat. Based on the known tryptic cleavage site of SSP, the in vivo generation of fibrils is presumably the result of premature trypsin activation.
authors.affiliation: Pancreatitis-Research Laboratory DL 36, Department of Visceral and Transplant Surgery, University Hospital Zürich, 8091, Zürich, Switzerland.
authors.forename: Severin
authors.initials: S
authors.lastname: Meili
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Marc
authors.initials: M
authors.lastname: Schiesser
authors.forename: Daniel
authors.initials: D
authors.lastname: Bimmler
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D022142:Secretory Vesicles / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D006360:Heat-Shock Proteins; D000073718:Pancreatitis-Associated Proteins; D020033:Protein Isoforms; C000612141:REG3A protein, human