Complement Component C5 Deficiency Reduces Edema Formation in Murine Ligation-Induced Acute Pancreatitis

Merriam, Louis T.; Webster, Cecile; Joehl, Raymond J.

doi:10.1006/jsre.1996.4916

Cited by 11 publications

(12 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Complement C3 may be involved in a variety of pathophysiological processes in chronic pancreatitis, including deposition at the basement membrane and inhibition by TGF-beta 77 . Significantly, C5 has been shown to have a role in edema formation in a mouse acute pancreatitis model 78 . In addition to their involvement in the pain pathway, both proteins have roles in fibrosis-related pathways, while complement C5 is also involved in inflammation pathways.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis (GeLC–MS/MS) of ePFT-Collected Pancreatic Fluid in Chronic Pancreatitis

et al. 2012

View full text Add to dashboard Cite

Chronic pancreatitis is characterized by inflammation, fibrosis, pain, and loss of exocrine function of the pancreas. We aimed to identify differentially-expressed proteins in the ePFT-collected pancreatic fluid from individuals with chronic pancreatitis (CP; n=9) and controls with chronic abdominal pain not associated with the pancreas (NP; n=9). Using GeLC-MS/MS techniques, we identified a total of 1391 different proteins in 18 pancreatic fluid samples. Of these proteins, 257 and 413 were identified exclusively in the control and chronic pancreatitis cohorts, respectively, and 721 were identified in both cohorts. Spectral counting and statistical analysis thereof revealed an additional 38 and 77 proteins that were up- or down-regulated, respectively, in the pancreatic fluid from individuals with chronic pancreatitis. As expected, gene ontology analysis illustrated that the largest percentage of differentially-regulated proteins was secreted/extracellular in origin. In addition, proteins that were down-regulated with statistical significance in the chronic pancreatitis cohort were determined to have biological function of proteases, corresponding to the canonical pancreatic insufficiency associated with chronic pancreatitis. Proteins enriched in pancreatic fluid from chronic pancreatitis patients had roles in fibrosis, inflammation, and pain, whereas digestive enzymes were significantly less abundant. Our workflow provided a mass spectrometry-based approach for the further study of the pancreatic fluid proteome which may lead to the discovery potential biomarkers of chronic pancreatitis.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis (GeLC–MS/MS) of ePFT-Collected Pancreatic Fluid in Chronic Pancreatitis

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Vice versa , in the absence of C5, C5-deficient mice develop significantly less pancreatic edema in the course of AP (53). …”

Section: Complement In the Pathophysiology Of Apmentioning

confidence: 99%

Complement in Pancreatic Disease—Perpetrator or Savior?

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

“…This is indicative of many redundancies of ligands and receptors characteristic of the cytokine and chemokine families. Gene knockout models have been used to determine the function of several specific targeted genes such as interleukin (IL)‐1 and tumour necrosis factor‐α70–73, IL‐6 74 , IL‐10 75 , chemoattractant cytokine receptor‐1 76 , neurokinin‐1 receptor 77, 78 , intercellular adhesion molecule‐1 (ICAM‐1) 79–81, metallothionein‐1 82 , cathepsin B 83 , mouse α2‐macroglobulin and murinoglobulin 84 , complement factor C5a 85, 86 , granulocyte‐macrophage colony‐stimulating factor 20 and phospholipase A 2 87 .…”

Section: Non‐invasive Models Of Acute Pancreatitismentioning

confidence: 99%

Review of experimental animal models of acute pancreatitis

Cuthbertson

Christophi

2006

HPB

128

105

View full text Add to dashboard Cite

The underlying mechanisms involved in the pathogenesis of acute pancreatitis are ill understood. The mortality rate of this disease has not significantly improved over the past few decades. Current treatment options are limited, and predominantly aimed at supportive therapy. A key feature of severe acute pancreatitis is the presence of extensive tissue necrosis with both local and systemic manifestations of inflammatory response syndromes. A better understanding of the underlying pathophysiology of severe acute pancreatitis may lead to more targeted therapeutic options, potentially leading to improved survival. Animal models of acute pancreatitis are therefore an essential investigative tool for these aims to be achieved. This review discusses the suitability of recent non-invasive models of acute pancreatitis such as hormone-induced, alcohol-induced, immune-mediated, diet-induced, gene knockout and L-arginine; and invasive models including closed duodenal loop, antegrade pancreatic duct perfusion, biliopancreatic duct injection, combination of secretory hyperstimulation with minimal intraductal bile acid exposure, vascular-induced, ischaemia/reperfusion and duct ligation.

show abstract

Complement Component C5 Deficiency Reduces Edema Formation in Murine Ligation-Induced Acute Pancreatitis

Cited by 11 publications

References 4 publications

Proteomic Analysis (GeLC–MS/MS) of ePFT-Collected Pancreatic Fluid in Chronic Pancreatitis

Proteomic Analysis (GeLC–MS/MS) of ePFT-Collected Pancreatic Fluid in Chronic Pancreatitis

Complement in Pancreatic Disease—Perpetrator or Savior?

Review of experimental animal models of acute pancreatitis

Contact Info

Product

Resources

About