PMN-elastase contributes to the severity of experimental acute pancreatitis via direct effects on acinar cells

Pancreatology ◽  
2012 ◽  
Vol 12 (6) ◽  
pp. 543-544
Author(s):  
Ali A. Aghdassi ◽  
Christian Storck ◽  
Matthias Sendler ◽  
Sudarshan Ravi Malla ◽  
Annett Günther ◽  
...  
Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1407 ◽  
Author(s):  
Michael Chvanov ◽  
Svetlana Voronina ◽  
Xiaoying Zhang ◽  
Svetlana Telnova ◽  
Robert Chard ◽  
...  

Acute pancreatitis is a frequent disease that lacks specific drug treatment. Unravelling the molecular mechanisms of acute pancreatitis is essential for the development of new therapeutics. Several inducers of acute pancreatitis trigger sustained Ca2+ increases in the cytosol and mitochondria of pancreatic acinar cells. The mitochondrial calcium uniporter (MCU) mediates mitochondrial Ca2+ uptake that regulates bioenergetics and plays an important role in cell survival, damage and death. Aberrant Ca2+ signaling and mitochondrial damage in pancreatic acinar cells have been implicated in the initiation of acute pancreatitis. The primary aim of this study was to assess the involvement of the MCU in experimental acute pancreatitis. We found that pancreatic acinar cells from MCU−/− mice display dramatically reduced mitochondrial Ca2+ uptake. This is consistent with the drastic changes of stimulus-metabolism coupling, manifested by the reduction of mitochondrial NADH/FAD+ responses to cholecystokinin and in the decrease of cholecystokinin-stimulated oxygen consumption. However, in three experimental models of acute pancreatitis (induced by caerulein, taurolithocholic acid 3-sulfate or palmitoleic acid plus ethanol), MCU knockout failed to reduce the biochemical and histological changes characterizing the severity of local and systemic damage. A possible explanation of this surprising finding is the redundancy of damaging mechanisms activated by the inducers of acute pancreatitis.


2003 ◽  
Vol 124 (4) ◽  
pp. A400
Author(s):  
Augusto Villanueva-Rodriguez ◽  
Julio Iglesias-Garcia ◽  
Jose Larino-Noia ◽  
Manuel Barreiro-Deacosta ◽  
Jose Iglesias-Canle ◽  
...  

2021 ◽  
Author(s):  
Samara Rodrigues Bonfim Damasceno Oliveira ◽  
Álvaro Xavier Franco ◽  
Marielle Pires Quaresma ◽  
Cecília Mendes Morais de Carvalho ◽  
Fabrícia da Cunha Jácome Marques ◽  
...  

Abstract Lectins isolated from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) are promising molecules to modulate cell death. Acute pancreatitis, characterized by acinar cell necrosis and inflammation, presents significant morbidity and mortality. This study has investigated the effects of ConA and ConBr on experimental acute pancreatitis and pancreatic acinar cell death induced by bile acid. Pancreatitis was induced by retrograde pancreatic ductal injection of 3% sodium taurocholate (Na-TC) in male Swiss mice. ConA or ConBr (0.1, 1 or 10 mg/kg) were intravenously applied to mice 1 h and 12 h after induction. After 24 hours, the severity of pancreatitis was evaluated by serum amylase and lipase, histopathological changes and myeloperoxidase assay. Pancreatic acinar cells were incubated with ConA (200 µg/ml) or ConBr (200 µg/ml) and taurolithocholic acid 3-sulfate (TLCS; 500 µM). Necrosis and changes in mitochondrial membrane potential (ΔѰm) were detected by fluorescence confocal microscopy. Treatment (post-insult) with ConA and ConBr decreased pancreatic damage caused by retrograde injection of Na-TC in mice, reducing pancreatic neutrophil infiltration, edema and necrosis. In addition, ConA and ConBr decreased pancreatic acinar cell necrosis and depolarization of ΔѰm caused by TLCS. The inhibition of necrosis was prevented by the lectin domain blockade; molecular docking analysis showed strong interaction of ConA and ConBr crystal structures with mannose residues. In conclusion, ConA and ConBr markedly inhibited in vitro and in vivo damage, effects partly dependent on the interaction with mannose residues on acinar cells. These data support the potential application of these proteins for treatment of acute pancreatitis.


Pancreas ◽  
1991 ◽  
Vol 6 (3) ◽  
pp. 253-259 ◽  
Author(s):  
Waldemar Uhl ◽  
Markus Büchler ◽  
Peter Malfertheiner ◽  
Markus Martini ◽  
Hans G. Beger

2020 ◽  
Vol 3 (1) ◽  
pp. 136-141
Author(s):  
Vijaykumar C Bada

Background: Acute pancreatitis (AP) is an inflammatory process with a highly variable clinical course. This study was conducted to compare the multifactor vs independent marker in predicting the severity of acute pancreatitis. Subjects and Methods: The present study comprised    of 50 patients of acute pancreatitis. In all patients, reactive protein (CRP), Interleukin-6 (IL-6), PMN-Elastase (PMN-E), Procalcitonin (PCT), RANSON”s score, GLASGOW score, APACHE-II score, APACHE-O score and Balthazar’s CTSI score was recorded. Results: There were 45 males and 5 females in the study. There were 12 (22.64%) obese patients in this study. The age of the patients was a significant indicator    to discriminate or predict patients with mild or severe pancreatitis. With an AUROC of 0.6004, it was found that age was a poor predictor       of the severity of acute pancreatitis. Obesity of the patients was a significant indicator to discriminate or predict patients with mild or severe pancreatitis. With an AUROC of 0.6004, it was found that age is a poor predictor of the severity of acute pancreatitis. Organ failure at admission is more likely to reflect severe cases, it is found to be a poor predictor of severity in acute pancreatitis. The mean CTSI score in the study was 3.57 (SD 2.64), with a median of 2 and ranged from 1 to 10. It was higher in severe pancreatitis and a CTSI score of >=3 was significantly associated with patients with acute pancreatitis by bivariate analysis. Conclusion: The authors found that overall, CRP was the best predictor, followed by IL-6, CTSI score, PCT, Glasgow, Ranson’s and APACHE-II. PMN-Elastase, Age, obesity and organ failure at admission are poor predictors of severity of acute pancreatitis.


2020 ◽  
Vol 3 (2) ◽  
pp. 1-4
Author(s):  
B. Jagan Mohan Reddy ◽  
S.P. Girish

Background: Acute pancreatitis is an inflammatory disease of the exocrine pancreas with rapid onset. The present study was conducted to assess the usefulness of CRP, PMN elastase, PCT and IL- 6 as prognostic factors in patients with acute pancreatitis. Subjects and Methods: The present study comprised 53 patients who presented with a diagnosis of Acute Pancreatitis. CRP was estimated by turbidimetric immunoassay using CRP/U2A-000 kit. PMN-Elastase was estimated by solid-phase enzyme immunoassay. Procalcitonin was estimated by the immuno- chromatographic test. IL-6 was estimated by Immuno-enzymatic assay. Results: There were 47 males and 6 females in the present study. The mean SD CRP in patients with mild pancreatitis was 44.35 53.04 and in severe pancreatitis was 174.80 14.55, PCT was seen in 4 in mild pancreatitis patients and 12 in severe pancreatitis patients, PMN- elastase level was 3.89 1087 in mild pancreatitis and 3.99 2.75 inn severe pancreatitis patients, IL-6 level was 129.63 319.08 in mild pancreatitis and 1166.76 818.06 in severe pancreatitis patients. The difference was significant (P< 0.05). CRP had higher (100) specificity as compared to PCT (81), PMN- E (10) and IL- 6 (90), Specificity found to be 88, 81, 97 and 94 respectively, PPV was 84, 74, 67 and 90 respectively, NPV was 100, 87, 62 and 94 respectively, accuracy was 92, 81, 62 and 92 respectively, AUC was 0.97, 0.81, 0.43 and 0.95 respectively. Conclusion: Authors found that CRP is the single best predictor of the severity of acute pancreatitis. IL-6 and PCT also are reliable predictors. PMN-Elastase needs to be assessed in patients with acute pancreatitis presenting early in the course of the illness.


1996 ◽  
Vol 76 (02) ◽  
pp. 184-186 ◽  
Author(s):  
Kenji lijima ◽  
Fumiyo Murakami ◽  
Yasushi Horie ◽  
Katsumi Nakamura ◽  
Shiro Ikawa ◽  
...  

SummaryA 74-year-old female developed pneumonia following herpes simplex encephalitis. Her white blood cell counts reached 28,400/μl, about 90% of which consisted of granulocytes. The polymorphonuclear (PMN) elastase/α1-arantitrypsin complex levels increased and reached the maximum of 5,019 ng/ml, indicating the release of a large amount of elastase derived from the granulocytes. The mechanism of PMN elastase release was most likely to be granulocyte destruction associated with phagocytosis. The cleavage of fibrinogen and fibrin by PMN elastase, independent of plasmin, was indicated by the presence of the fragments in immunoprecipitated plasma from the patient corresponding to elastase-induced FDP D and DD fragments and the absence of fragments corresponding to plasmin-induced FDP D and DD fragments on SDS-PAGE. These findings suggested that the large amount of PMN elastase released from the excessive numbers of granulocytes in this patient with herpes simplex encephalitis and pneumonia, induced the cleavage of fibrinogen and fibrin without the participation of plasmin.


Sign in / Sign up

Export Citation Format

Share Document