The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP/regI and PAP/regIII

Abstract

// Theresia Reding 1, * , Cristian Palmiere 2, * , Clinsyjos Pazhepurackel 1 , Marc Schiesser 1 , Daniel Bimmler 1 , Andrea Schlegel 1 , Ursula Süss 1 , Sabrina Steiner 1 , Leandro Mancina 1 , Gitta Seleznik 1 , Rolf Graf 1 1 Department of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland 2 Department of Legal Medicine, Lausanne, Switzerland * These authors contributed equally to this work Correspondence to: Rolf Graf, email: Rolf.graf@usz.ch Keywords: sepsis, acute phase reaction, regenerating proteins, pancreas, intestine Received: February 07, 2017      Accepted: March 08, 2017      Published: March 16, 2017 ABSTRACT Introduction: In patients with infection and sepsis serum levels of Pancreatic Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP during these conditions is presumably the pancreas, however, an intestinal origin cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was identified in the pancreas. These proteins were also localized in intestinal organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal models of sepsis and in healthy humans. Results: PSP and PAP responded to remote lesions in rats although the pancreatic response was much more pronounced than the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content in the pancreas compared to any other organ while PAP was most abundant in the small intestine. Both proteins responded to CLP or sham operation in the pancreas. PSP also increased in the intestine during CLP. The distribution of PSP and PAP in human tissue mirrored the distribution in the murine models. Materials and methods: Distribution of PSP and PAP was visualized by immunohistochemistry. Rats and mice underwent midline laparotomies followed by mobilization of tissue and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture (CLP) procedures or sham laparotomies were performed. Human tissue extracts were analyzed for PSP and PAP. Conclusions: The pancreas reacts to remote lesions and septic insults in mice and rats with increased PSP synthesis, while PAP is selectively responsive to septic events. Furthermore, our results suggest that serum PSP in septic patients is predominantly derived through an acute phase response of the pancreas.