Complement system in sodium taurocholate pancreatitis in the rat

Seelig, R; Lankisch, P. G.; Koop, H.; Winckler, K.; Kaboth, U; Seelig, H. P.

doi:10.1007/bf01851939

Cited by 18 publications

(8 citation statements)

References 17 publications

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“…Only severe necrotizing pancreatitis, but not mild edematous AP, in rats was accompanied by early complement activation with increased levels of C3a (48). Similar results linking decreasing complement hemolytic activity (CH50), acinar C3 deposits, and histological tissue damage could be found in a rodent model of AP (49). It is noteworthy that complement consumption in early AP can be accompanied by persistently lowered serum complement levels several weeks after the onset of symptoms (50).…”

Section: Complement In the Pathophysiology Of Apsupporting

confidence: 78%

Complement in Pancreatic Disease—Perpetrator or Savior?

et al. 2017

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The complement system is a major pillar of the humoral innate immune system. As a first line of defense against pathogens, it mediates early inflammatory response and links different branches of humoral and cellular immunity. Disorders affecting the exocrine pancreas, such as acute pancreatitis, potentially lead to a life-threatening systemic inflammatory response with aberrant activation of complement and coagulation cascades. Pancreatic proteases can activate key effectors of the complement system, which in turn drive local and systemic inflammation. Beyond that, the extent of pancreas–complement interaction covers complex pro- and anti-inflammatory mechanisms, which to this day remain to be fully elucidated. This review provides a comprehensive overview of the pathophysiological role of complement in diseases of the exocrine pancreas, based on existing experimental and clinical data. Participation of complement in acute and chronic pancreatitis is addressed, as well as its role in tumor immunology. Therapeutic strategies targeting complement in these diseases have long been proposed but have not yet arrived in the clinical setting.

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Section: Complement In the Pathophysiology Of Apsupporting

confidence: 78%

Complement in Pancreatic Disease—Perpetrator or Savior?

et al. 2017

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“…In sodium taurocholate pancreatitis, edema and necroses develop early in the disease, followed by leukocyte infiltration [32]. According to Wanke [33], bile salt-induced pancreatitis develops in two stages.…”

Section: Discussionmentioning

confidence: 99%

When should treatment of acute experimental pancreatitis be started?

et al. 1988

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Sodium taurocholate pancreatitis in the rat is a frequently used experimental model for evaluating therapeutical regimes in this disease. It is, however, uncertain when treatment should be started, as the early phase of this experimental model and thus the time when the pancreatitis really develops is unknown. Serum and pancreatic enzymes, as well as pancreatic morphology, were therefore studied 5, 30, and 60 min after induction of sodium taurocholate pancreatitis. It was found that increase in serum enzymes and decrease in pancreatic enzymes and morphological changes characteristic for acute pancreatitis develop as early as 5 and 30 min after induction of pancreatitis. Thus, therapy in this model may be started shortly after induction of acute pancreatitis.

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“…Accumulating data suggest that the complement system exerts important roles in several diverse processes. In addition to its classical role in microbial defense, complement can recruit neutrophils and regulate inflammation and tissue damage in different inflammatory conditions [11][12][13][14][15]. C3 is the central molecule of complement, positioned at the crossroad of all the complement activation pathways.…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that trypsin can cleave C3 and facilitate leukocyte activation [16]. Deposition of C3 on acinar cells and histological damage of acinar cells were shown to increase in the taurocholate-induced model of AP [11]. In addition, in an endotoxin model of brain injury, C3-deficient mice exhibited decreased neutrophil recruitment and endothelial activation [15].…”

Section: Introductionmentioning

confidence: 99%

Complement Component 3 Is Required for Tissue Damage, Neutrophil Infiltration, and Ensuring NET Formation in Acute Pancreatitis

et al. 2020

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Background: Neutrophil extracellular traps (NETs) are known to play an important role in the pathophysiology of acute pancreatitis (AP). Activation of the complement cascade has been shown to occur in AP. The aim of this study was to examine whether complement component 3 is involved in the generation of NETs in AP. Methods: AP was induced in wild-type and C3-deficient mice by retrograde infusion of taurocholate into the pancreatic duct. Blood, lung, and pancreas tissue were collected and MPO activity was determined in lung and pancreas tissue. Histological examination of the inflamed pancreas was performed. Plasma levels of CXCL2, MMP-9, IL-6, and DNA-histone complexes as well as pancreatic levels of CXCL1 and CXCL2 were determined by use of enzyme-linked immunosorbent assay. NETs were detected in the pancreas by electron microscopy. The amount of MPO and citrullinated histone 3 in neutrophils isolated from bone marrow was examined using flow cytometry. Results: In C3-deficient mice, challenge with taurocholate yielded much fewer NETs in the pancreatic tissue compared with wild-type controls. Taurocholate-induced blood levels of amylase, tissue injury, and neutrophil recruitment in the pancreas were markedly reduced in the mice lacking C3. Furthermore, MPO levels in the lung, and plasma levels of IL-6, MMP-9, and CXCL2 were significantly lower in the C3-deficient mice compared to wild-type mice after the induction of AP. In vitro studies revealed that neutrophils from C3-deficient mice had normal NET-forming ability and recombinant C3a was not capable of directly inducing NETs formation in the wild-type neutrophils. Conclusion: C3 plays an important role in the pathophysiology of AP as it is necessary for the recruitment of neutrophils into the pancreas and ensuring NETs formation. Targeting C3 could hence be a potential strategy to ameliorate local damage as well as remote organ dysfunction in AP.

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Complement system in sodium taurocholate pancreatitis in the rat

Cited by 18 publications

References 17 publications

Complement in Pancreatic Disease—Perpetrator or Savior?

Complement in Pancreatic Disease—Perpetrator or Savior?

When should treatment of acute experimental pancreatitis be started?

Complement Component 3 Is Required for Tissue Damage, Neutrophil Infiltration, and Ensuring NET Formation in Acute Pancreatitis

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