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Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis.

Abdulla, Aree, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
Awla, Darbaz, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
Thorlacius, Henrik, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
visa fler...
Regnér, Sara, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
visa färre...
2011
Engelska.
Ingår i: Journal of Leukocyte Biology. - John Wiley and Sons Ltd. - 1938-3673. ; 90, s. 975-982
  • Tidskriftsartikel (refereegranskat)
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  • The relationship between inflammation and proteolytic activation in pancreatitis is an unresolved issue in pancreatology. The purpose of this study was to define the influence of neutrophils on trypsinogen activation in severe AP. Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. For neutrophil depletion, an anti-Gr-1 antibody was administered before pancreatitis induction. Administration of the anti-Gr-1 antibody reduced circulating neutrophils by 97%. Pancreatic TAP and serum amylase levels increased 2 h and 24 h after induction of pancreatitis. Neutrophil depletion reduced pancreatic TAP and serum amylase levels at 24 h but not at 2 h after pancreatitis induction. Pancreatic MPO and infiltration of neutrophils, as well as MIP-2 levels, were increased 24 h after taurocholate infusion. Two hours after taurocholate administration, no significant pancreatic infiltration of neutrophils was observed. Injection of the anti-Gr-1 antibody abolished MPO activity, neutrophil accumulation, and MIP-2 levels, as well as acinar cell necrosis, hemorrhage, and edema in the pancreas at 24 h. Moreover, taurocholate-provoked tissue damage and MPO activity in the lung were normalized by neutrophil depletion. Intravital fluorescence microscopy revealed a 97% reduction of leukocytes in the pancreatic microcirculation after administration of the anti-Gr-1 antibody. Our data demonstrate that initial trypsinogen activation is independent of neutrophils, whereas later activation is dependent on neutrophils in the pancreas. Neutrophils are critical in mediating pancreatic and lung tissue damage in severe AP.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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Abdulla, Aree
Awla, Darbaz
Thorlacius, Henr ...
Regnér, Sara
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MEDICIN OCH HÄLSOVETENSKAP
MEDICIN OCH HÄLS ...
och Medicinska grund ...
och Cell och molekyl ...
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Journal of Leuko ...
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Lunds universitet

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