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. 1989 Feb;134(2):315–326.

Experimental acute pancreatitis induced by platelet activating factor in rabbits.

G Emanuelli 1, G Montrucchio 1, E Gaia 1, L Dughera 1, G Corvetti 1, L Gubetta 1
PMCID: PMC1879574  PMID: 2464939

Abstract

This study indicates that a single injection of platelet activating factor (PAF, 50-500 ng) into the superior pancreaticoduodenal artery of rabbits induces dose-dependent morphologic alterations of pancreatic tissue and increases serum amylase levels, both consistent with the development of an acute pancreatitis. The main histologic findings observed by light microscopy 24-72 hours after the injection of PAF were edema, polymorphonuclear neutrophil infiltration, cell vacuolization, and acinar cell necrosis. Fat cell necrosis was present in 30% of animals. By electron microscopy an increase of the number of zymogen granules in the apical region of acinar cells was observed 3 hours after PAF challenge. At 24-72 hours, many acinar cells showed vacuoles containing myelinlike figures, zymogen granules, and cellular debris. Pancreatic lesions developed in the area supplied by the artery injected with PAF and they were completely antagonized by the pretreatment of rabbits with CV 3988, a specific antagonist of PAF. In addition, the significant protective effect of atropine suggests a potential role for cholinergic mechanisms in the pancreatic alterations induced by PAF.

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Selected References

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

  1. Alloatti G., Montrucchio G., Mariano F., Tetta C., De Paulis R., Morea M., Emanuelli G., Camussi G. Effect of platelet-activating factor (PAF) on human cardiac muscle. Int Arch Allergy Appl Immunol. 1986;79(1):108–112. doi: 10.1159/000233953. [DOI] [PubMed] [Google Scholar]
  2. Ardlie N. G., Packham M. A., Mustard J. F. Adenosine diphosphate-induced platelet aggregation in suspensions of washed rabbit platelets. Br J Haematol. 1970 Jul;19(1):7–17. doi: 10.1111/j.1365-2141.1970.tb01596.x. [DOI] [PubMed] [Google Scholar]
  3. Benveniste J., Henson P. M., Cochrane C. G. Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. J Exp Med. 1972 Dec 1;136(6):1356–1377. doi: 10.1084/jem.136.6.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bessin P., Bonnet J., Apffel D., Soulard C., Desgroux L., Pelas I., Benveniste J. Acute circulatory collapse caused by platelet-activating factor (PAF-acether) in dogs. Eur J Pharmacol. 1983 Jan 21;86(3-4):403–413. doi: 10.1016/0014-2999(83)90190-5. [DOI] [PubMed] [Google Scholar]
  5. Bonnet J., Loiseau A. M., Orvoen M., Bessin P. Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes. Agents Actions. 1981 Dec;11(6-7):559–562. doi: 10.1007/BF01978740. [DOI] [PubMed] [Google Scholar]
  6. Camussi G., Aglietta M., Coda R., Bussolino F., Piacibello W., Tetta C. Release of platelet-activating factor (PAF) and histamine. II. The cellular origin of human PAF: monocytes, polymorphonuclear neutrophils and basophils. Immunology. 1981 Feb;42(2):191–199. [PMC free article] [PubMed] [Google Scholar]
  7. Camussi G., Aglietta M., Malavasi F., Tetta C., Piacibello W., Sanavio F., Bussolino F. The release of platelet-activating factor from human endothelial cells in culture. J Immunol. 1983 Nov;131(5):2397–2403. [PubMed] [Google Scholar]
  8. Camussi G., Alloatti G., Montrucchio G., Meda M., Emanuelli G. Effect of platelet activating factor on guinea-pig papillary muscle. Experientia. 1984 Jul 15;40(7):697–699. doi: 10.1007/BF01949729. [DOI] [PubMed] [Google Scholar]
  9. Camussi G., Bussolino F., Tetta C., Piacibello W., Aglietta M. Biosynthesis and release of platelet-activating factor from human monocytes. Int Arch Allergy Appl Immunol. 1983 Mar;70(3):245–251. doi: 10.1159/000233331. [DOI] [PubMed] [Google Scholar]
  10. Camussi G., Pawlowski I., Tetta C., Roffinello C., Alberton M., Brentjens J., Andres G. Acute lung inflammation induced in the rabbit by local instillation of 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine or of native platelet-activating factor. Am J Pathol. 1983 Jul;112(1):78–88. [PMC free article] [PubMed] [Google Scholar]
  11. Camussi G., Tetta C., Bussolino F., Caligaris Cappio F., Coda R., Masera C., Segoloni G. Mediators of immune-complex-induced aggregation of polymorphonuclear neutrophils. II. Platelet-activating factor as the effector substance of immune-induced aggregation. Int Arch Allergy Appl Immunol. 1981;64(1):25–41. doi: 10.1159/000232671. [DOI] [PubMed] [Google Scholar]
  12. Camussi G., Tetta C., Coda R., Segoloni G. P., Vercellone A. Platelet-activating factor-induced loss of glomerular anionic charges. Kidney Int. 1984 Jan;25(1):73–81. doi: 10.1038/ki.1984.10. [DOI] [PubMed] [Google Scholar]
  13. Chignard M., Le Couedic J. P., Tence M., Vargaftig B. B., Benveniste J. The role of platelet-activating factor in platelet aggregation. Nature. 1979 Jun 28;279(5716):799–800. doi: 10.1038/279799a0. [DOI] [PubMed] [Google Scholar]
  14. Gonzalez-Crussi F., Hsueh W. Experimental model of ischemic bowel necrosis. The role of platelet-activating factor and endotoxin. Am J Pathol. 1983 Jul;112(1):127–135. [PMC free article] [PubMed] [Google Scholar]
  15. Halonen M., Palmer J. D., Lohman I. C., McManus L. M., Pinckard R. N. Differential effects of platelet depletion on the physiologic alterations of IgE anaphylaxis and acetyl glyceryl ether phosphorylcholine infusion in the rabbit. Am Rev Respir Dis. 1981 Oct;124(4):416–421. doi: 10.1164/arrd.1981.124.4.416. [DOI] [PubMed] [Google Scholar]
  16. Halonen M., Palmer J. D., Lohman I. C., McManus L. M., Pinckard R. N. Respiratory and circulatory alterations induced by acetyl glyceryl ether phosphorylcholine, a mediator of IgE anaphylaxis in the rabbit. Am Rev Respir Dis. 1980 Dec;122(6):915–924. doi: 10.1164/arrd.1980.122.6.915. [DOI] [PubMed] [Google Scholar]
  17. Heymann M. A., Payne B. D., Hoffman J. I., Rudolph A. M. Blood flow measurements with radionuclide-labeled particles. Prog Cardiovasc Dis. 1977 Jul-Aug;20(1):55–79. doi: 10.1016/s0033-0620(77)80005-4. [DOI] [PubMed] [Google Scholar]
  18. Humphrey D. M., Hanahan D. J., Pinckard R. N. Induction of leukocytic infiltrates in rabbit skin by acetyl glyceryl ether phosphorylcholine. Lab Invest. 1982 Sep;47(3):227–234. [PubMed] [Google Scholar]
  19. Humphrey D. M., McManus L. M., Hanahan D. J., Pinckard R. N. Morphologic basis of increased vascular permeability induced by acetyl glyceryl ether phosphorylcholine. Lab Invest. 1984 Jan;50(1):16–25. [PubMed] [Google Scholar]
  20. Humphrey D. M., McManus L. M., Satouchi K., Hanahan D. J., Pinckard R. N. Vasoactive properties of acetyl glyceryl ether phosphorylcholine and analogues. Lab Invest. 1982 Apr;46(4):422–427. [PubMed] [Google Scholar]
  21. Issekutz A. C., Szpejda M. Evidence that platelet activating factor may mediate some acute inflammatory responses. Studies with the platelet-activating factor antagonist, CV3988. Lab Invest. 1986 Mar;54(3):275–281. [PubMed] [Google Scholar]
  22. Jones R. T., Garcia J. H., Mergner W. J., Pendergrass R. E., Valigorsky J. M., Trump B. F. Effects of shock on the pancreatic acinar cell. Cellular and subcellular effects in humans. Arch Pathol. 1975 Dec;99(12):634–644. [PubMed] [Google Scholar]
  23. Lampel M., Kern H. F. Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch A Pathol Anat Histol. 1977 Mar 11;373(2):97–117. doi: 10.1007/BF00432156. [DOI] [PubMed] [Google Scholar]
  24. Leff A. R., White S. R., Munoz N. M., Popovich K. J., Shioya T., Stimler-Gerard N. P. Parasympathetic involvement in PAF-induced contraction in canine trachealis in vivo. J Appl Physiol (1985) 1987 Feb;62(2):599–605. doi: 10.1152/jappl.1987.62.2.599. [DOI] [PubMed] [Google Scholar]
  25. Levi R., Burke J. A., Guo Z. G., Hattori Y., Hoppens C. M., McManus L. M., Hanahan D. J., Pinckard R. N. Acetyl glyceryl ether phosphorylcholine (AGEPC). A putative mediator of cardiac anaphylaxis in the guinea pig. Circ Res. 1984 Feb;54(2):117–124. doi: 10.1161/01.res.54.2.117. [DOI] [PubMed] [Google Scholar]
  26. Lotner G. Z., Lynch J. M., Betz S. J., Henson P. M. Human neutrophil-derived platelet activating factor. J Immunol. 1980 Feb;124(2):676–684. [PubMed] [Google Scholar]
  27. McManus L. M., Pinckard R. N. Kinetics of acetyl glyceryl ether phosphorylcholine (AGEPC)-induced acute lung alterations in the rabbit. Am J Pathol. 1985 Oct;121(1):55–68. [PMC free article] [PubMed] [Google Scholar]
  28. Mencia-Huerta J. M., Benveniste J. Platelet-activating factor and macrophages. I. Evidence for the release from rat and mouse peritoneal macrophages and not from mastocytes. Eur J Immunol. 1979 May;9(5):409–415. doi: 10.1002/eji.1830090512. [DOI] [PubMed] [Google Scholar]
  29. Muirhead E. E., Byers L. W., Desiderio D. M., Brooks B., Brosius W. M. Antihypertensive lipids from the kidney: alkyl ether analogs of phosphatidylcholine. Fed Proc. 1981 Jun;40(8):2285–2290. [PubMed] [Google Scholar]
  30. Neutze J. M., Wyler F., Rudolph A. M. Use of radioactive microspheres to assess distribution of cardiac output in rabbits. Am J Physiol. 1968 Aug;215(2):486–495. doi: 10.1152/ajplegacy.1968.215.2.486. [DOI] [PubMed] [Google Scholar]
  31. Oates P. S., Bruce N. W., Morgan R. G. Pancreatic blood flow in the rat during enlargement, involution, and cholecystokinin treatment. Am J Physiol. 1984 Nov;247(5 Pt 1):G457–G462. doi: 10.1152/ajpgi.1984.247.5.G457. [DOI] [PubMed] [Google Scholar]
  32. Pinckard R. N., Farr R. S., Hanahan D. J. Physicochemical and functional identity of rabbit platelet-activating factor (PAF) released in vivo during IgE anaphylaxis with PAF released in vitro from IgE sensitized basophils. J Immunol. 1979 Oct;123(4):1847–1857. [PubMed] [Google Scholar]
  33. Pirotzky E., Bidault J., Burtin C., Gubler M. C., Benveniste J. Release of platelet-activating factor, slow-reacting substance, and vasoactive amines from isolated rat kidneys. Kidney Int. 1984 Feb;25(2):404–410. doi: 10.1038/ki.1984.31. [DOI] [PubMed] [Google Scholar]
  34. Prescott S. M., Zimmerman G. A., McIntyre T. M. Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3534–3538. doi: 10.1073/pnas.81.11.3534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rosam A. C., Wallace J. L., Whittle B. J. Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature. 1986 Jan 2;319(6048):54–56. doi: 10.1038/319054a0. [DOI] [PubMed] [Google Scholar]
  36. Savion N., Selinger Z. Morphological changes in rat pancreatic slices associated with inhibition of enzyme secretion by high concentrations of secretagogues. J Cell Biol. 1978 Feb;76(2):467–482. doi: 10.1083/jcb.76.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shaw J. O., Pinckard R. N., Ferrigni K. S., McManus L. M., Hanahan D. J. Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycerol-3-phosphorylcholine (platelet activating factor). J Immunol. 1981 Sep;127(3):1250–1255. [PubMed] [Google Scholar]
  38. Steer M. L., Meldolesi J., Figarella C. Pancreatitis. The role of lysosomes. Dig Dis Sci. 1984 Oct;29(10):934–938. doi: 10.1007/BF01312483. [DOI] [PubMed] [Google Scholar]
  39. Söling H. D., Eibl H., Fest W. Acetylcholine-like effects of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine ('platelet-activating factor') and its analogues in exocrine secretory glands. Eur J Biochem. 1984 Oct 1;144(1):65–72. doi: 10.1111/j.1432-1033.1984.tb08431.x. [DOI] [PubMed] [Google Scholar]
  40. Söling H. D., Fest W. Synthesis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) in exocrine glands and its control by secretagogues. J Biol Chem. 1986 Oct 25;261(30):13916–13922. [PubMed] [Google Scholar]
  41. Terashita Z., Tsushima S., Yoshioka Y., Nomura H., Inada Y., Nishikawa K. CV-3988 - a specific antagonist of platelet activating factor (PAF). Life Sci. 1983 Apr 25;32(17):1975–1982. doi: 10.1016/0024-3205(83)90049-8. [DOI] [PubMed] [Google Scholar]
  42. Yasaka T., Boxer L. A., Baehner R. L. Monocyte aggregation and superoxide anion release in response to formyl-methionyl-leucyl-phenylalanine (FMLP) and platelet-activating factor (PAF). J Immunol. 1982 May;128(5):1939–1944. [PubMed] [Google Scholar]

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