期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 90, 期 5, 页码 975-982出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0411195
关键词
amylase; chemokines; inflammation; protease
资金
- Kurdistan regional government
- Nanakali group
- Swedish Medical Research Council [2009-4872]
- Crafoord Foundation
- Einar and Inga Nilsson Foundation
- Harald and Greta Jaensson Foundation
- Greta and Johan Kock Foundation
- Froken Agnes Nilsson Foundation
- Franke and Margareta Bergqvists Cancer Foundation
- Lundgren Foundation
- Magnus Bergvall Foundation
- Mossfelt Foundation
- Nanna Svartz Foundation
- Ruth and Richard Julin Foundation
- UMAS Cancer Foundation
- UMAS Foundations
- UMAS
- Lund University
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. J. Leukoc. Biol. 90: 975-982; 2011.
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