Pathophysiological role of platelets in acute experimental pancreatitis: influence of endothelin A receptor blockade

Uhlmann, Dirk; Lauer, Heike; Serr, F.; Ludwig, Stefan; Tannapfel, Andrea; Fiedler, Georg Martin; Hauss, Johann; Witzigmann, Helmut

doi:10.1007/s00441-006-0319-9

Cited by 10 publications

(4 citation statements)

References 45 publications

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“…Endothelin-1, a potent vasoconstrictor, was shown to be up-regulated in pancreatic endothelial cells by inflammatory stimuli, including cytokines, thrombin, and trypsin, which was associated with impaired splanchnic microcirculation in SAP [95]. Inhibition of endothelin receptor A attenuated reduced functional capillary density associated with experimental SAP in rats, and ameliorated platelet-endothelial and leukocyte-endothelial cell interactions, reducing numbers of stagnant platelets and leukocytes in pancreatic postcapillary venules [96]. PAF is a pleiotropic phospholipid mediator, with roles in hemostasis (platelet activation), endothelial cell activation (increase of capillary permeability), and inflammation (induction of cytokines, including IL-1β, TNF-α and IL-6) [97].…”

Section: Vascular Involvement In Acute Pancreatitismentioning

confidence: 99%

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The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Dumnicka

Maduzia

Ceranowicz

et al. 2017

IJMS

154

113

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Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

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Section: Vascular Involvement In Acute Pancreatitismentioning

confidence: 99%

“…Platelets enhance leukocyte rolling, sticking and transmigration in pancreatic venules in the early phase of AP [96,166]. Platelet P-selectin appears crucial for leukocyte recruitment and rolling in inflamed venules of the pancreas [167,168].…”

Section: Disturbances Of Hemostasis In Relation To Inflammation Inmentioning

confidence: 99%

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Dumnicka

Maduzia

Ceranowicz

et al. 2017

IJMS

154

113

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“…Similarly to TRALI, platelets appear to play a significant role in the induction of pancreatitis. Several observations indicate increased platelet activity in the above‐mentioned pathology . They also participate in neutrophil activation, migration, and complex formation with themselves .…”

Section: Discussionmentioning

confidence: 99%

“…Several observations indicate increased platelet activity in the abovementioned pathology. [50][51][52] They also participate in neutrophil activation, migration, and complex formation with themselves. 53,54 Therefore, pancreatitis appears to share certain pathophysiological features similar to that of ALI/TRALI.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the CD40/CD40L complex protects mice against ALI‐induced pancreas degradation

et al. 2019

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BACKGROUND Acute lung injury (ALI) is a severe complication of transfusion. In a previous study, we saw that inhibition of the CD40/CD40L complex allowed restoration of ALI lesions in an experimental mouse model. OBJECTIVES This study focused on pancreas‐associated injury development during experimental ALI pathogenesis and its limitation through CD40/CD40L complex inhibition. MATERIALS AND METHODS An ALI mouse model was established through intraperitoneal lipopolysaccharide and intravenous anti–major histocompatibility complex class I monoclonal antibody injection. Preemption of lesions was achieved with intravenous injection of neutralizing anti‐CD40L monoclonal antibody 30 minutes before the trigger, that is, anti–major histocompatibility complex class I monoclonal antibody administration. Histology and immunoassay analyses were used to evaluate pancreatic lesions. RESULTS ALI development induced significant degradation of the lungs and pancreas and was associated with pancreatic lesions. Different scores were established showing more severe injury to the pancreas in ALI conditions; however, injury was significantly reduced through CD40/CD40L complex inhibition. CONCLUSION This study supports the idea that several organs are exposed during ALI development, and particularly when such experimental ALI aims at mimicking transfusion‐associated ALI; nevertheless, preventive treatment inhibiting CD40/CD40L (sCD40L) complex formation provides protection from lung disease as well as disease of other organs.

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CD40L is not involved in acute experimental pancreatitis

Abdulla

Awla

Jeppsson

et al. 2011

European Journal of Pharmacology

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Pathophysiological role of platelets in acute experimental pancreatitis: influence of endothelin A receptor blockade

Cited by 10 publications

References 45 publications

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Inhibition of the CD40/CD40L complex protects mice against ALI‐induced pancreas degradation

CD40L is not involved in acute experimental pancreatitis

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