Journal Mobile Options
Table of Contents
Vol. 1, No. 4, 2001
Issue release date: 2001

From Acinar Cell Damage to Systemic Inflammatory Response: Current Concepts in Pancreatitis

Weber C.K. · Adler G.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Acute pancreatitis represents a local inflammatory disorder with severe systemic consequences. Significant progress in understanding the pathophysiology of acute pancreatitis has been achieved in recent years. However, there is no clear concept about initialization and propagation of the disease both in experimental models and in humans. Furthermore, reliable strategies to evaluate prognosis and perform therapy are still missing. The review focuses on mechanisms originating from acinar cells leading to a systemic inflammatory response in experimental pancreatitis.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Chiari H: Über die Selbstverdauung des menschlichen Pankreas. Z Heilkunde 1896;17:69–96.
  2. Weber CK, Adler G: Acute pancreatitis. Curr Opin Gastroenterol 2001, in press.
  3. Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK Jr, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD: Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996;14:141–145.
  4. Whitcomb DC, Preston RA, Aston CE, Sossenheimer MJ, Barua PS, Zhang Y, Wong-Chong A, White GJ, Wood PG, Gates LK Jr, Ulrich C, Martin SP, Post JC, Ehrlich GD: A gene for hereditary pancreatitis maps to chromosome 7q35. Gastroenterology 1996;110:1975–1980.
  5. Whitcomb DC: Early trypsinogen activation in acute pancreatitis. Gastroenterology 1999;116:770–772.
  6. Raraty M, Ward J, Erdemli G, Vaillant C, Neoptolemos JP, Sutton R, Petersen OH: Calcium-dependent enzyme activation and vacuole formation in the apical granular region of pancreatic acinar cells. Proc Natl Acad Sci USA 2000;97:12126–13131.
  7. Parekh AB: Calcium signaling and acute pancreatitis: Specific response to a promiscuous messenger. Proc Natl Acad Sci USA 2000;97:12933–12934.
  8. Jungermann J, Lerch MM, Weidenbach H, Lutz MP, Kruger B, Adler G: Disassembly of rat pancreatic acinar cell cytoskeleton during supramaximal secretagogue stimulation. Am J Physiol 1995;268:G328–G338.

    External Resources

  9. Fallon MB, Gorelick FS, Anderson JM, Mennone A, Saluja A, Steer ML: Effect of cerulein hyperstimulation on the paracellular barrier of rat exocrine pancreas. Gastroenterology 1995;108:1863–1872.
  10. Steinle AU, Weidenbach H, Wagner M, Adler G, Schmid RM: NF-kappaB/Rel activation in cerulein pancreatitis. Gastroenterology 1999;116:420–430.
  11. Neoptolemos JP, Kemppainen EA, Mayer JM, Fitzpatrick JM, Raraty MG, Slavin J, Beger HG, Hietaranta AJ, Puolakkainen PA: Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: A multicentre study. Lancet 2000;355:1955–1960.
  12. Hofbauer B, Saluja AK, Lerch MM, Bhagat L, Bhatia M, Lee HS, Frossard JL, Adler G, Steer ML: Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats. Am J Physiol 1998;275:G352–G362.

    External Resources

  13. Otani T, Chepilko SM, Grendell JH, Gorelick FS: Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis. Am J Physiol 1998;275:G999–G1009.

    External Resources

  14. Saluja AK, Donovan EA, Yamanaka K, Yamaguchi Y, Hofbauer B, Steer ML: Cerulein-induced in vitro activation of trypsinogen in rat pancreatic acini is mediated by cathepsin B. Gastroenterology 1997;113:304–310.
  15. Halangk W, Lerch MM, Brandt-Nedelev B, Roth W, Ruthenbuerger M, Reinheckel T, Domschke W, Lippert H, Peters C, Deussing J: Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J Clin Invest 2000;106:773–781.
  16. Krüger B, Albrecht E, Lerch MM: The role of intracellular calcium signaling in premature protease activation and the onset of pancreatitis. Am J Pathol 2000;157:43–50.
  17. Aberle H, Schwartz H, Kemler R: Cadherin-catenin complex:protein interactions and their implications for cadherin function. J Cell Biochem 1996;61:514–523.
  18. Lerch MM, Lutz MP, Weidenbach H, Muller-Pillasch F, Gress TM, Leser J, Adler G: Dissociation and reassembly of adherens junctions during experimental acute pancreatitis. Gastroenterology 1997;113:1355–1366.
  19. Leser J, Beil MF, Musa OA, Adler G, Lutz MP: Regulation of adherens junction protein p120(ctn) by 10 nM CCK precedes actin breakdown in rat pancreatic acini. Am J Physiol Gastrointest Liver Physiol 2000;278:G486–G491.

    External Resources

  20. Schmid RM, Adler G: NF-kappaB/rel/IkappaB: Implications in gastrointestinal diseases. Gastroenterology 2000;118:1208–1228.
  21. Tando Y, Algul H, Wagner M, Weidenbach H, Adler G, Schmid RM: Caerulein-induced NF-kappaB/Rel activation requires both Ca2+ and protein kinase C as messengers. Am J Physiol 1999;277:G678–G686.
  22. Baumann B, Weber CK, Troppmair J, Whiteside S, Israel A, Rapp UR, Wirth T: Raf induces NF-kappaB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation. Proc Natl Acad Sci USA 2000;97:4615–4620.
  23. Zaninovic V, Gukovskaya AS, Gukovsky I, Mouria M, Pandol SJ: Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells. J Physiol Gastrointest Liver Physiol 2000;279:G666–G676.

    External Resources

  24. Malka D, Vasseur S, Bodeker H, Ortiz EM, Dusetti NJ, Verrando P, Dagorn JC, Iovanna JL: Tumor necrosis factor alpha triggers antiapoptotic mechanisms in rat pancreatic cells through pancreatitis-associated protein I activation. Gastroenterology 2000;119:816–828.

    External Resources

  25. Gukovskaya AS, Gukovsky I, Zaninovic V, Song M, Sandoval D, Gukovsky S, Pandol SJ: Pancreatic acinar cells produce, release, and respond to tumor necrosis factor-alpha. Role in regulating cell death and pancreatitis. J Clin Invest 1997;100:1853–1862.
  26. Gloor B, Blinman TA, Rigberg DA, Todd KE, Lane JS, Hines OJ, Reber HA: Kupffer cell blockade reduces hepatic and systemic cytokine levels and lung injury in hemorrhagic pancreatitis in rats. Pancreas 2000;21:414–420.
  27. Kusske AM, Rongione AJ, Reber HA: Cytokines and acute pancreatitis. Gastroenterology 1996;110:639–642.
  28. Gerard C, Frossard JL, Bhatia M, Saluja A, Gerard NP, Lu B, Steer M: Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury. J Clin Invest 1997;100:2022–2027.
  29. Bachem MG, Schneider E, Gross H, Weidenbach H, Schmid RM, Menke A, Siech M, Beger H, Grunert A, Adler G: Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology 1998;115:421–432.
  30. Andoh A, Takaya H, Saotome T, Shimada M, Hata K, Araki Y, Nakamura F, Shintani Y, Fujiyama Y, Bamba T: Cytokine regulation of chemokine (IL-8, MCP-1 and Rantes) gene expression in human pancreatic periacinar myofibroblasts. Gastroenterology 2000;119:211–219.
  31. Rinderknecht H: Fatal pancreatitis, a consequence of excessive leukocyte stimulation? Int J Pancreatol 1988;3:105–112.
  32. Bhatia M, Saluja AK, Hofbauer B, Lee HS, Frossard JL, Steer ML: The effect of neutrophil depletion on a completely noninvasive model of acute pancreatitis-associated lung injury. Int J Pancreatol 1998;24:77–83.
  33. Kyriakides C, Jasleen J, Wang Y, Moore FD Jr, Ashley SW, Hechtman HB: Neutrophils, not complement, mediate the mortality of experimental hemorrhagic pancreatitis. Pancreas 2001;22:40–46.
  34. Frossard JL, Saluja A, Bhagat L, Lee HS, Bhatia M, Hofbauer B, Steer ML: The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury. Gastroenterology 1999;116:694–701.
  35. Demols A, Le Moine O, Desalle F, Quertinmont E, Van Laethem JL, Deviere J: CD4+ T cells play an important role in acute experimental pancreatitis in mice. Gastroenterology 2000;118:582–590.
  36. Okazaki K, Uchida K, Ohana M, Nakase H, Uose S, Inai M, Matsushima Y, Katamura K, Ohmori K, Chiba T: Autoimmune-related pancreatitis is associated with auto-antibodies and a Th1/Th2-type cellular immune response. Gastroenterology 2000;118:573–581.
  37. Hartl FU: Molecular chaperones in protein folding. Nature 1996;381:571–580.
  38. Riabowol KT, Mizzen LA, Welch WJ: Heat shock is lethal to fibroblasts with antibodies against HSP70. Science 1988;242:433–436.
  39. Weber CK, Gress T, Muller-Pillasch F, Lerch MM, Weidenbach H, Adler G: Supramaximal secretagogue stimulation enhances heat shock protein expression in the rat pancreas. Pancreas 1995;10:360–367.

    External Resources

  40. Grise K, Kim F, McFadden D: Hyperthermia induces heat-shock protein expression, reduces pancreatic injury, and improves survival in necrotizing pancreatitis. Pancreas 2000;21:120–125.
  41. Weber H, Wagner AC, Jonas L, Merkord J, Hofken T, Nizze H, Leitzmann P, Goke B, Schuff-Werner P: Heat shock response is associated with protection against acute interstitial pancreatitis in rats. Dig Dis Sci 2000;45:2252–2264.

    External Resources

  42. Lee HS, Bhagat L, Frossard JL, Hietaranta A, Singh VP, Steer ML, Saluja AK: Water immersion stress induces heat shock protein 60 expression and protects against pancreatitis in rats. Gastroenterology 2000;119:220–229.
  43. Bhagat L, Singh VP, Hietaranta AJ, Agrawal S, Steer ML, Saluja AK: Heat shock protein 70 prevents secretagogue-induced cell injury in the pancreas by preventing intracellular trypsinogen activation. J Clin Invest 2000;106:81–89.
  44. Hietaranta AJ, Singh VP, Bhagat L, van Acker GJ, Song AM, Mykoniatis A, Steer ML, Saluja AK: Water immersion stress prevents caerulein-induced pancreatic acinar cell NF-kB activation by attenuating caerulein-induced intracellular Ca2+ changes. J Biol Chem 2001;276:18742–18747.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50