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240. FAS-LIGAND PROTECTS ISLET CELLS FROM APOPTOSIS IN CHRONIC PANCREATITIS
  1. A.C. Bateman1,
  2. K.S.A. Thomas1,
  3. D.R. Fine2,
  4. P.A. Johnson2,
  5. C.D. Johnson3,
  6. J.P. Iredale2
  1. 1Pancreatic & Liver Fibrosis Research Groups, Dept of Histopathology, 2Division of Cell and Molecular Medicine, and 3University Dept of Surgery, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
  1. R.A. Al-Mufti,
  2. R.C.N. Williamson,
  3. R.T. Mathie
  1. Division of Surgery, Anaesthetics & Intensive Care, Hammersmith Hospital, Imperial College School of Medicine, London W12 0NN, UK

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Background: Exocrine (acinar) destruction and endocrine (islet) preservation in chronic pancreatitis (CP) is related to differential apoptotic indices within these cellular compartments.

Aim: To define the role of cell cycle regulatory proteins in the control of pancreatic epithelial cell apoptosis.

Methods: Formalin-fixed, paraffin-embedded tissue from six cases of CP and eight normal controls (N) were studied using immunohistochemistry for BCl-2, Bax, retinoblastoma protein (Rb) and Fas ligand (Fas-L). Labelling patterns were assessed using semi-quantitative (intensity-proportion [I-P]) or fully quantitative (labelling index [LI]) analysis.

Results: Rb protein was expressed at a higher level by acinar cells in CP than N (mean acinar cell Rb LI 1.45% in CP and 0.437% in N; p<0.05) but this difference was not observed within islet cells. BCl-2 was more strongly expressed by acinar than islet cells in CP and N (e.g. N mean BCl-2 I-P score 4.88 in acini and 0.375 in islets; p<0.05) while Bax was strongly expressed by a subset of islet cells and weakly by centroacinar cells (e.g. N mean Bax I-P score 1.75 in acini and 4.31 in islets; p<0.05). Fas-L was more strongly expressed by islet than acinar cells in CP and N (e.g. CP mean Fas-L I-P score 5.67 in islets and 2.83 in acini; p<0.01).

Conclusion: Strong BCl-2 expression by acinar cells and of Bax by islet cells was an unexpected result and indicates complex control of apoptosis within these cell populations. Increased Rb protein expression by acinar cells in CP may differentially promote apoptosis within these cells. Fas-L expression by islet cells may protect islets from apoptosis by promoting apoptosis of cytotoxic T-lymphocytes.

241. THE EFFECT OF SELECTIVE INHIBITION OF INDUCIBLE NITRIC OXIDE SYNTHASE ON THE OUTCOME OF SEVERE ACUTE PANCREATITIS

Background: Nitric oxide (NO), overproduced by inducible NO synthase (iNOS), has been established as a key inflammatory mediator in systemic inflammatory response syndrome leading to multiple organ failure.

Aim: To examine the effect of …

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