Development of radioimmunoassays for free tetra-L-aspartyl-L-lysine trypsinogen activation peptides (TAP)

Hurley, Paul R.; Cook, Alistair J.; Jehanli, Ahmed; Austen, Brian; Hermon‐Taylor, John

doi:10.1016/0022-1759(88)90127-5

Cited by 88 publications

(25 citation statements)

References 11 publications

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“…Trypsinogen activation peptide (TAP) concentrations in pancreatic lobules were detected by a method as previously described [8, 19]. In brief, pancreatic lobules were boiled in 200 m M Tris-HCl and 20 m M EDTA, pH 7.3, for 15 min at 100°C and homogenized for 30 s. The resulting homogenates were centrifuged at 1,500 rpm for 10 min at 4°C and the supernatants were taken for an enzyme immunoassay using Biotrin TAP EIA kit (Biotrin International, Sinsheim-Reihen, Germany).…”

Section: Methodsmentioning

confidence: 99%

Induction of IκB-Kinase by Cholecystokinin Is Mediated by Trypsinogen Activation in Rat Pancreatic Lobules

Tando

Algül²,

Schneider³

et al. 2002

Digestion

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Background and Aims: Supramaximal concentrations of cholecystokinin (CCK) or cerulein induce the intracellular activation of trypsinogen and the transcription factor NF-ĸB, a key regulator of inflammatory gene expression. Both events occur early in the development of an acute pancreatitis. The aim of this study was to examine the relationship between intracellular trypsinogen and NF-ĸB activation. Methods: We detected NF-ĸB-binding activity in electromobility shift assays, IĸB proteolysis in Western analysis and endogenous IĸB-kinase (IKKα and β) activation using immune complex kinase assays following treatment with CCK in rat pancreatic lobules. To block intrapancreatic trypsinogen activation, a potent and cell-permeable serine-protease inhibitor, Pefabloc, was used. Results: CCK-induced IĸBα degradation and subsequent NF-ĸB activation correlated closely with the catalytic activity of IKKs to phosphorylate IĸBα in vitro. Activation is dose-dependent and peaked at 30 min. Doses of Pefabloc sufficient to inhibit trypsin activation reduced CCK-induced activation of NF-ĸB whereas TNF-α-induced NF-ĸB activation was not blocked but slightly increased. Moreover, treatment with Pefabloc as well as another serine protease inhibitor, FUT175, inhibited CCK-induced IKK activation. Conclusion: These results suggest that intrapancreatic activation of trypsinogen may contribute to NF-ĸB signaling via IKK activation in cerulein pancreatitis. This also explains the fact that only doses of CCK which activate trypsinogen induce NF-ĸB activation in pancreatic acinar cells. Thus, trypsinogen activation is likely to modulate signaling events in acinar cells in the initial phase of acute pancreatitis.

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Section: Methodsmentioning

confidence: 99%

Induction of IκB-Kinase by Cholecystokinin Is Mediated by Trypsinogen Activation in Rat Pancreatic Lobules

Tando

Algül²,

Schneider³

et al. 2002

Digestion

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“…For the measurement of the zymogen activation peptides TAP and PROP, a Tr-FIA was developed based on an ELISA developed by Hurley et al [9]. …”

Section: Methodsmentioning

confidence: 99%

“…On activation of anionic trypsinogen, the activation peptide Ala-Pro-phe-(Asp) 4 -Lys is cleaved at the N-terminus of the zymogen. Antibodies against the highly conserved amino acid sequence (Asp) 4 -Lys (D 4 K) of the trypsinogen activation peptide (TAP) [8, 9]enable measurement of this peptide in body fluids. High levels of TAP have been found in the ascites and urine of patients with acute pancreatitis correlating well with the extent of pancreatic necroses [4, 10, 11].…”

Section: Introductionmentioning

confidence: 99%

Local and Systemic Zymogen Activation in Human Acute Pancreatitis

Mayer

Rau²,

Siech³

et al. 2000

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Background: Activation of trypsinogen and phospholipase A₂ is an early event in pancreatic inflammation, but little is known about zymogen activation and the severity of human pancreatitis. Methods: Using a new fluoroimmunoassay we measured trypsinogen activation peptide (TAP) and phospholipase A₂ activation peptide (PROP) in plasma and ascites in 25 patients with acute pancreatitis. TAP, PROP, Pro-PROP and pancreatic PLA₂-I were measured in plasma for 14 days and in pancreatic necroses, ascitic fluid and pleural effusions. Results: All 16 patients with severe acute pancreatitis (SAP) had pancreatic necrosis, 10 developed systemic complications like sepsis, pulmonary or renal failure, 6 had infected necrosis, and 4 died. All 9 patients with mild pancreatitis (MAP) survived. Plasma TAP on admission was higher in patients with SAP than in those with MAP and increased in infected necroses. It did not correlate with systemic complications. Systemic PROP was not increased in complicated courses but was significantly higher in patients with MAP than in those with SAP on admission. Pro-PROP was higher in patients with SAP than in those with MAP but was not correlated with systemic complications. Plasma pancreatic PLA₂-I was increased but not different in patients with SAP and those with MAP. In patients with pancreatic necrosis, TAP and PROP were highest, while in those with post-acute pancreatic abscess, only PROP and Pro-PROP were high. In patients with pleural effusion, TAP was low and PROP/ Pro-PROP were high. Conclusion: Trypsinogen and PLA₂-I activation are early events in acute pancreatitis and the activation peptides can be detected in plasma. In the pancreas, trypsinogen activation is accompanied by PLA₂-I activation in patients with pancreatic necrosis. However, in our study, organ complications in SAP patients was not associated with increased plasma PROP.

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“…dimethyl prostaglandin E, is also infused intravenously, AOP becomes acute haemorrhagic pancreatitis (AHP). We previously showed that dopamine reduced the severity of AHP when administered within 12 The results are shown in Table II. In this Serum lipase activities at 24 hours were not significantly increased from basal values in both groups 6 and 7.…”

Section: *5 (Interquartile Range (Iqr)4) In Groups 2mentioning

confidence: 89%

Dopamine in models of alcoholic acute pancreatitis.

Karanjia

Widdison

Lutrin

et al. 1994

Gut

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Acute oedematous pancreatitis and acute haemorrhagic pancreatitis were studied using the low pressure duct perfusion models of alcoholic pancreatitis in cats. After creating either form over 24 hours, each pancreas was histologically graded and assigned an inflammatory score (0-16; absent-severe (IQR 2, p<0 05 v group 1), and in group 4 it was 7 (IQR 4, p<0 05 v group 1). This was matched by significantly lower levels of urinary tripsinogen activation peptide at 24 hours. In experiment 2 (group 5) we tried to reduce microvascular permeability further by combining dopamine with antihistamines, but there was no improvement in the inflammatory score. As oedematous pancreatitis is the commoner and milder form of acute pancreatitis in clinical practice, in experiment 3 we looked at the effect ofdopamine in this model. In group 6 control cats (no treatment), the inflammatory score was 7 (IQR 3, p<0 05 v group 1). In group 7 cats given dopamine (5 ,ug/kg.min for six hours) from 12 hours after the onset of acute oedematous pancreatitis, the inflammatory score was reduced to 4 (IQR 2, p<0 05 v group 6). This was matched by a significant reduction in the 24 hour urinary tripsin activation peptide concentration. (Gut 1994; 35: 547-55 Here, in a further progression of these experiments, we analysed three more issues. In experiment 1 we examined the effect ofvarying the dose of dopamine in the original model of alcoholic AHP. In experiment 2 we investigated whether the addition of the H,/H, blockers, diphenhydramine and cimetidine, might have a synergistic effect if combined with dopamine as these latter agents would be expected to reduce microvascular permeability by an action through different receptors. In experiment 3 we investigated the effect of dopamine in the model of alcoholic AOP because in humans alcohol often leads to the milder oedematous form of acute pancreatitis. Methods THE MODELSThe models have been described in detail previously"A and are considered briefly here.Alcoholic AOP Fasted cats were anaesthetised and after drawing samples for estimating basal serum lipase and urinary tripsinogen activation peptide (TAP), a laparotomy was performed. The body of the stomach was cannulated with the tip of the cannula sited in the antrum. The main pancreatic duct was cannulated in the tail of the pancreas with plastic tubing that had previously been filled with a physiological salt solution (standard per-

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Development of radioimmunoassays for free tetra-L-aspartyl-L-lysine trypsinogen activation peptides (TAP)

Cited by 88 publications

References 11 publications

Induction of IκB-Kinase by Cholecystokinin Is Mediated by Trypsinogen Activation in Rat Pancreatic Lobules

Induction of IκB-Kinase by Cholecystokinin Is Mediated by Trypsinogen Activation in Rat Pancreatic Lobules

Local and Systemic Zymogen Activation in Human Acute Pancreatitis

Dopamine in models of alcoholic acute pancreatitis.

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