Skip to main content
NCBI home page
Gut logoLink to Gut
. 1996 May;38(5):747–752. doi: 10.1136/gut.38.5.747

Lipopolysaccharide induced apoptosis of rat pancreatic acinar cells.

V J Laine 1, K M Nyman 1, H J Peuravuori 1, K Henriksen 1, M Parvinen 1, T J Nevalainen 1
PMCID: PMC1383159  PMID: 8707123

Abstract

BACKGROUND--Bacterial lipopolysaccharide (LPS) has been proposed to participate in the pathogenesis of pancreatic inflammatory disease. AIMS--This study investigated the role of endotoxaemia in the pathogenesis of pancreatic acinar cell injury. METHODS--Sixty eight male Spraque-Dawley rats were used in the study. Escherichia coli LPS (5 mg/kg) was injected into the peritoneal cavity of the rats. The concentration of pancreatic phospholipase A2 (PLA2) in plasma was measured and pancreatic tissue examined by histology, in situ detection of free DNA 3'-ends, and electrophoretic DNA analysis. RESULTS--The concentration of pancreatic PLA2 increased in plasma and the catalytic activity of PLA2 increased in pancreatic tissue after an LPS injection. Apoptosis in pancreatic acinar cells and fragmentation of DNA typical of apoptosis in pancreatic tissue was seen 24 hours after an LPS injection. Pancreatic acinar atrophy was seen 72 hours after the LPS injection. CONCLUSIONS--These data show that LPS causes release of pancreatic PLA2 into blood plasma, activation of PLA2 in pancreatic tissue, and apoptosis of acinar cells.

Full text

PDF
747

Images in this article

749Figure 3
on p.749
750Figure 4
on p.750
750Figure 5
on p.750

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agarwal M. L., Larkin H. E., Zaidi S. I., Mukhtar H., Oleinick N. L. Phospholipase activation triggers apoptosis in photosensitized mouse lymphoma cells. Cancer Res. 1993 Dec 15;53(24):5897–5902. [PubMed] [Google Scholar]
  2. Billig H., Furuta I., Hsueh A. J. Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology. 1993 Nov;133(5):2204–2212. doi: 10.1210/endo.133.5.8404672. [DOI] [PubMed] [Google Scholar]
  3. Boggs S. S., Boggs D. R., Joyce R. A. Response to endotoxin of endotoxin-"resistant" C3H/HeJ mice: a model for study of hematopoietic control. Blood. 1980 Mar;55(3):444–452. [PubMed] [Google Scholar]
  4. Bomalaski J. S., Clark M. A. Phospholipase A2 and arthritis. Arthritis Rheum. 1993 Feb;36(2):190–198. doi: 10.1002/art.1780360208. [DOI] [PubMed] [Google Scholar]
  5. Davidson F. F., Dennis E. A. Evolutionary relationships and implications for the regulation of phospholipase A2 from snake venom to human secreted forms. J Mol Evol. 1990 Sep;31(3):228–238. doi: 10.1007/BF02109500. [DOI] [PubMed] [Google Scholar]
  6. Eskola J. U., Nevalainen T. J., Lövgren T. N. Time-resolved fluoroimmunoassay of human pancreatic phospholipase A2. Clin Chem. 1983 Oct;29(10):1777–1780. [PubMed] [Google Scholar]
  7. Exley A. R., Leese T., Holliday M. P., Swann R. A., Cohen J. Endotoxaemia and serum tumour necrosis factor as prognostic markers in severe acute pancreatitis. Gut. 1992 Aug;33(8):1126–1128. doi: 10.1136/gut.33.8.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fabris C., Basso D., Panozzo M. P., Del Favero G., Meggiato T., Plebani M., Ferrara C., Fogar P., Zaninotto M., Naccarato R. Urinary phospholipase A2 excretion in chronic pancreatic diseases. Int J Pancreatol. 1992 Jun;11(3):179–184. doi: 10.1007/BF02924183. [DOI] [PubMed] [Google Scholar]
  9. Foulis A. K., Murray W. R., Galloway D., McCartney A. C., Lang E., Veitch J., Whaley K. Endotoxaemia and complement activation in acute pancreatitis in man. Gut. 1982 Aug;23(8):656–661. doi: 10.1136/gut.23.8.656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Funakoshi A., Yamada Y., Ito T., Ishikawa H., Yokota M., Shinozaki H., Wakasugi H., Misaki A., Kono M. Clinical usefulness of serum phospholipase A2 determination in patients with pancreatic diseases. Pancreas. 1991 Sep;6(5):588–594. doi: 10.1097/00006676-199109000-00013. [DOI] [PubMed] [Google Scholar]
  11. Gianotti L., Munda R., Alexander J. W., Tchervenkov J. I., Babcock G. F. Bacterial translocation: a potential source for infection in acute pancreatitis. Pancreas. 1993 Sep;8(5):551–558. [PubMed] [Google Scholar]
  12. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  13. Gustafson-Svärd C., Tagesson C., Boll R. M., Kald B. Tumor necrosis factor-alpha potentiates phospholipase A2-stimulated release and metabolism of arachidonic acid in cultured intestinal epithelial cells (INT 407). Scand J Gastroenterol. 1993 Apr;28(4):323–330. doi: 10.3109/00365529309090250. [DOI] [PubMed] [Google Scholar]
  14. Hiefinger-Schindlbeck R. T., Dasser C., Hübner-Parajsz C., Hoffmann G. E., Guder W. G. Differentiation of human phospholipase A2 isoenzymes in serum and other body fluids with use of monoclonal antibodies. Eur J Clin Chem Clin Biochem. 1993 Apr;31(4):211–215. doi: 10.1515/cclm.1993.31.4.211. [DOI] [PubMed] [Google Scholar]
  15. Hietaranta A. J., Aho H. J., Nevalainen T. J. Pancreatic phospholipase A2 in cerulein-induced acute pancreatitis in the rat. Int J Pancreatol. 1993 Dec;14(3):261–267. doi: 10.1007/BF02784935. [DOI] [PubMed] [Google Scholar]
  16. Hirano T., Manabe T., Imanishi K., Tobe T. Protective effect of a cephalosporin, Shiomarin, plus a new potent protease inhibitor, E3123, on rat taurocholate-induced pancreatitis. J Gastroenterol Hepatol. 1993 Jan-Feb;8(1):52–59. doi: 10.1111/j.1440-1746.1993.tb01175.x. [DOI] [PubMed] [Google Scholar]
  17. Hoeck W. G., Ramesha C. S., Chang D. J., Fan N., Heller R. A. Cytoplasmic phospholipase A2 activity and gene expression are stimulated by tumor necrosis factor: dexamethasone blocks the induced synthesis. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4475–4479. doi: 10.1073/pnas.90.10.4475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Horne W. I., Tsukamoto H. Dietary modulation of alcohol-induced pancreatic injury. Alcohol. 1993 Nov-Dec;10(6):481–484. doi: 10.1016/0741-8329(93)90069-z. [DOI] [PubMed] [Google Scholar]
  19. Kazacos E. A., Van Vleet J. F. Sequential ultrastructural changes of the pancreas in zinc toxicosis in ducklings. Am J Pathol. 1989 Mar;134(3):581–595. [PMC free article] [PubMed] [Google Scholar]
  20. Kortesuo P. T., Hietaranta A. J., Jämiä M., Hirsimäki P., Nevalainen T. J. Rat pancreatic phospholipase A2. Purification, localization, and development of an enzyme immunoassay. Int J Pancreatol. 1993 Apr;13(2):111–118. doi: 10.1007/BF02786079. [DOI] [PubMed] [Google Scholar]
  21. Mangan D. F., Welch G. R., Wahl S. M. Lipopolysaccharide, tumor necrosis factor-alpha, and IL-1 beta prevent programmed cell death (apoptosis) in human peripheral blood monocytes. J Immunol. 1991 Mar 1;146(5):1541–1546. [PubMed] [Google Scholar]
  22. Nevalainen T. J., Eskola J. U., Aho A. J., Havia V. T., Lövgren T. N., Näntö V. Immunoreactive phospholipase A2 in serum in acute pancreatitis and pancreatic cancer. Clin Chem. 1985 Jul;31(7):1116–1120. [PubMed] [Google Scholar]
  23. Peng B., Raveche E. Apoptosis induction in CD5+(Ly1+) malignant B cells. Leukemia. 1993 Jun;7(6):789–794. [PubMed] [Google Scholar]
  24. Pfeilschifter J., Mühl H., Pignat W., Märki F., van den Bosch H. Cytokine regulation of group II phospholipase A2 expression in glomerular mesangial cells. Eur J Clin Pharmacol. 1993;44 (Suppl 1):S7–S9. doi: 10.1007/BF01428384. [DOI] [PubMed] [Google Scholar]
  25. Rao M. S., Yeldandi A. V., Subbarao V., Reddy J. K. Role of apoptosis in copper deficiency-induced pancreatic involution in the rat. Am J Pathol. 1993 Jun;142(6):1952–1957. [PMC free article] [PubMed] [Google Scholar]
  26. Ribeiro J. M., Carson D. A. Ca2+/Mg(2+)-dependent endonuclease from human spleen: purification, properties, and role in apoptosis. Biochemistry. 1993 Sep 7;32(35):9129–9136. doi: 10.1021/bi00086a018. [DOI] [PubMed] [Google Scholar]
  27. Robaye B., Dumont J. E. Phospholipase A2 activity is not involved in the tumor necrosis factor-triggered apoptotic DNA fragmentation in bovine aortic endothelial cells. Biochem Biophys Res Commun. 1992 Nov 16;188(3):1312–1317. doi: 10.1016/0006-291x(92)91374-y. [DOI] [PubMed] [Google Scholar]
  28. Santavuori S. A., Kortesuo P. T., Eskola J. U., Nevalainen T. J. Application of a new monoclonal antibody for time-resolved fluoroimmunoassay of human pancreatic phospholipase A2. Eur J Clin Chem Clin Biochem. 1991 Dec;29(12):819–826. [PubMed] [Google Scholar]
  29. Shakir K. M. Phospholipase A2 activity of post-heparin plasma: a rapid and sensitive assay and partial characterization. Anal Biochem. 1981 Jun;114(1):64–70. doi: 10.1016/0003-2697(81)90452-8. [DOI] [PubMed] [Google Scholar]
  30. Shi L., Kam C. M., Powers J. C., Aebersold R., Greenberg A. H. Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. J Exp Med. 1992 Dec 1;176(6):1521–1529. doi: 10.1084/jem.176.6.1521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Simons R. K., Maier R. V., Chi E. Y. Pulmonary effects of continuous endotoxin infusion in the rat. Circ Shock. 1991 Apr;33(4):233–243. [PubMed] [Google Scholar]
  32. Suffys P., Beyaert R., De Valck D., Vanhaesebroeck B., Van Roy F., Fiers W. Tumour-necrosis-factor-mediated cytotoxicity is correlated with phospholipase-A2 activity, but not with arachidonic acid release per se. Eur J Biochem. 1991 Jan 30;195(2):465–475. doi: 10.1111/j.1432-1033.1991.tb15727.x. [DOI] [PubMed] [Google Scholar]
  33. Sulkowski U., Boin C., Brockmann J., Bünte H. The influence of caecostomy and colonic irrigation on pathophysiology and prognosis in acute experimental pancreatitis. Eur J Surg. 1993 May;159(5):287–291. [PubMed] [Google Scholar]
  34. Tilly J. L., Hsueh A. J. Microscale autoradiographic method for the qualitative and quantitative analysis of apoptotic DNA fragmentation. J Cell Physiol. 1993 Mar;154(3):519–526. doi: 10.1002/jcp.1041540310. [DOI] [PubMed] [Google Scholar]
  35. Ulich T. R., Guo K., Yin S., del Castillo J., Yi E. S., Thompson R. C., Eisenberg S. P. Endotoxin-induced cytokine gene expression in vivo. IV. Expression of interleukin-1 alpha/beta and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation. Am J Pathol. 1992 Jul;141(1):61–68. [PMC free article] [PubMed] [Google Scholar]
  36. Vanhaesebroeck B., Reed J. C., De Valck D., Grooten J., Miyashita T., Tanaka S., Beyaert R., Van Roy F., Fiers W. Effect of bcl-2 proto-oncogene expression on cellular sensitivity to tumor necrosis factor-mediated cytotoxicity. Oncogene. 1993 Apr;8(4):1075–1081. [PubMed] [Google Scholar]
  37. Walker N. I., Winterford C. M., Williamson R. M., Kerr J. F. Ethionine-induced atrophy of rat pancreas involves apoptosis of acinar cells. Pancreas. 1993 Jul;8(4):443–449. doi: 10.1097/00006676-199307000-00007. [DOI] [PubMed] [Google Scholar]
  38. Wallig M. A., Jeffery E. H. Enhancement of pancreatic and hepatic glutathione levels in rats during cyanohydroxybutene intoxication. Fundam Appl Toxicol. 1990 Jan;14(1):144–159. doi: 10.1016/0272-0590(90)90240-k. [DOI] [PubMed] [Google Scholar]
  39. Yamamoto C., Yoshida S., Taniguchi H., Qin M. H., Miyamoto H., Mizuguchi Y. Lipopolysaccharide and granulocyte colony-stimulating factor delay neutrophil apoptosis and ingestion by guinea pig macrophages. Infect Immun. 1993 May;61(5):1972–1979. doi: 10.1128/iai.61.5.1972-1979.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zhang Y. H., Takahashi K., Jiang G. Z., Kawai M., Fukada M., Yokochi T. In vivo induction of apoptosis (programmed cell death) in mouse thymus by administration of lipopolysaccharide. Infect Immun. 1993 Dec;61(12):5044–5048. doi: 10.1128/iai.61.12.5044-5048.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES