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Absence of the neutrophil serine protease cathepsin G decreases neutrophil granulocyte infiltration but does not change the severity of acute pancreatitis

Identifieur interne : 000B20 ( Main/Exploration ); précédent : 000B19; suivant : 000B21

Absence of the neutrophil serine protease cathepsin G decreases neutrophil granulocyte infiltration but does not change the severity of acute pancreatitis

Auteurs : Ali A. Aghdassi [Allemagne] ; Daniel S. John [Allemagne] ; Matthias Sendler [Allemagne] ; Christian Storck [Allemagne] ; Cindy Van Den Brandt [Allemagne] ; Burkhard Krüger [Allemagne] ; Frank Ulrich Weiss [Allemagne] ; Julia Mayerle [Allemagne] ; Markus M. Lerch [Allemagne]

Source :

RBID : PMC:6856518

Abstract

Acute pancreatitis is characterized by an early intracellular protease activation and invasion of leukocytes into the pancreas. Cathepsins constitute a large group of lysosomal enzymes, that have been shown to modulate trypsinogen activation and neutrophil infiltration. Cathepsin G (CTSG) is a neutrophil serine protease of the chymotrypsin C family known to degrade extracellular matrix components and to have regulatory functions in inflammatory disorders. The aim of this study was to investigate the role of CTSG in pancreatitis. Isolated acinar cells were exposed to recombinant CTSG and supramaximal cholezystokinin stimulation. In CTSG−/− mice and corresponding controls acute experimental pancreatitis was induced by serial caerulein injections. Severity was assessed by histology, serum enzyme levels and zymogen activation. Neutrophil infiltration was quantified by chloro-acetate ersterase staining and myeloperoxidase measurement. CTSG was expessed in inflammatory cells but not in pancreatic acinar cells. CTSG had no effect on intra-acinar-cell trypsinogen activation. In CTSG−/− mice a transient decrease of neutrophil infiltration into the pancreas and lungs was found during acute pancreatitis while the disease severity remained largely unchanged. CTSG is involved in pancreatic neutrophil infiltration during pancreatitis, albeit to a lesser degree than the related neutrophil (PMN) elastase. Its absence therefore leaves pancreatitis severity essentially unaffected.


Url:
DOI: 10.1038/s41598-019-53293-0
PubMed: 31727956
PubMed Central: 6856518


Affiliations:


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<p id="Par1">Acute pancreatitis is characterized by an early intracellular protease activation and invasion of leukocytes into the pancreas. Cathepsins constitute a large group of lysosomal enzymes, that have been shown to modulate trypsinogen activation and neutrophil infiltration. Cathepsin G (CTSG) is a neutrophil serine protease of the chymotrypsin C family known to degrade extracellular matrix components and to have regulatory functions in inflammatory disorders. The aim of this study was to investigate the role of CTSG in pancreatitis. Isolated acinar cells were exposed to recombinant CTSG and supramaximal cholezystokinin stimulation. In CTSG
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<sup>−/−</sup>
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<name sortKey="Nannuru, Kc" uniqKey="Nannuru K">KC Nannuru</name>
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<name sortKey="Futakuchi, M" uniqKey="Futakuchi M">M Futakuchi</name>
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<author>
<name sortKey="Sadanandam, A" uniqKey="Sadanandam A">A Sadanandam</name>
</author>
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<name sortKey="Singh, Rk" uniqKey="Singh R">RK Singh</name>
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<name sortKey="Lerch, Mm" uniqKey="Lerch M">MM Lerch</name>
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<name sortKey="Halangk, W" uniqKey="Halangk W">W Halangk</name>
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<name sortKey="Niederau, C" uniqKey="Niederau C">C Niederau</name>
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<name sortKey="Ferrell, Ld" uniqKey="Ferrell L">LD Ferrell</name>
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<author>
<name sortKey="Grendell, Jh" uniqKey="Grendell J">JH Grendell</name>
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<name sortKey="John, Daniel S" sort="John, Daniel S" uniqKey="John D" first="Daniel S." last="John">Daniel S. John</name>
<name sortKey="Kruger, Burkhard" sort="Kruger, Burkhard" uniqKey="Kruger B" first="Burkhard" last="Krüger">Burkhard Krüger</name>
<name sortKey="Lerch, Markus M" sort="Lerch, Markus M" uniqKey="Lerch M" first="Markus M." last="Lerch">Markus M. Lerch</name>
<name sortKey="Mayerle, Julia" sort="Mayerle, Julia" uniqKey="Mayerle J" first="Julia" last="Mayerle">Julia Mayerle</name>
<name sortKey="Sendler, Matthias" sort="Sendler, Matthias" uniqKey="Sendler M" first="Matthias" last="Sendler">Matthias Sendler</name>
<name sortKey="Storck, Christian" sort="Storck, Christian" uniqKey="Storck C" first="Christian" last="Storck">Christian Storck</name>
<name sortKey="Van Den Brandt, Cindy" sort="Van Den Brandt, Cindy" uniqKey="Van Den Brandt C" first="Cindy" last="Van Den Brandt">Cindy Van Den Brandt</name>
<name sortKey="Weiss, Frank Ulrich" sort="Weiss, Frank Ulrich" uniqKey="Weiss F" first="Frank Ulrich" last="Weiss">Frank Ulrich Weiss</name>
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