Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tryptases”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMed1997

Human mucus protease inhibitor in airway fluids is a potential defensive compound against infection with influenza A and Sendai viruses.

Tryptase Clara, a trypsin-like protease localized exclusively in and secreted from Clara cells to the bronchial epithelium of rat, proteolytically activates the infectivity of influenza A virus [H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma (1992) J. Biol. Chem. 267, 13573-13579]. We report here that human mucus protease inhibitor (MPI), a major inhibitor of granulocyte elastase in the lining fluids of the human respiratory tract, significantly inhibited proteolytic activation of the infectivity of influenza A and Sendai viruses by tryptase Clara in vitro and multi-cycles of mouse-adapted influenza A virus replication in rat lungs in vitro. Recombinant MPI and the C- but not the N-terminal domain of the MPI inhibited both the proteolytic activity of tryptase Clara and the activation of virus infection. The 50% inhibitory concentrations of recombinant MPI and the C-terminal domain for tryptase Clara with Sendai virus envelope glycoprotein as substrate were 7.4 and 61.6 nM, respectively. These results indicate that MPI is a defensive compound against virus infection. Since there is evidence suggesting that concentrations of MPI in respiratory fluids are insufficient for prevention of virus infection, administration of MPI in the airway may be useful for treatment of these virus infections.

Animals↗
PubMed2006

Allergen cleavage by effector cell-derived proteases regulates allergic inflammation.

The key event of allergic inflammation, allergen-induced crosslinking of mast cell-bound IgE antibodies, is accompanied by release of inflammatory mediators, cytokines, and proteases, in particular beta-tryptase. We provide evidence that protease-mediated cleavage of allergens represents a mechanism that regulates allergen-induced mast cell activation. When used in molar ratios as they occur in vivo, purified beta-tryptase cleaved major grass and birch pollen allergens, resulting in defined peptide fragments as mapped by mass spectrometry. Tryptase-cleaved allergens showed reduced IgE reactivity and allergenic activity. The biological relevance is demonstrated by the fact that lysates from activated human mast cells containing tryptase levels as they occur in vivo cleaved allergens. Additionally, protamine, an inhibitor of heparin-dependent effector cell proteases, augmented allergen-induced release of mediators from effector cells. Protease-mediated allergen cleavage may represent an important mechanism for terminating allergen-induced effector cell activation.

Allergens↗
PubMed2001

Different patterns of mast cell activation by muscle relaxants in human skin.

BACKGROUND: Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects. METHODS: Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves. RESULTS: For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase. CONCLUSIONS: Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.

Adult↗
PubMed1999

Evidence of mast cell activity in the middle ears of children with otitis media with effusion.

OBJECTIVES: This is the first study to report the presence of tryptase, a reflection of mast cell activity, in chronic middle ear effusion of patients whose atopic status was characterized. DESIGN AND METHODS: Mediator activity of mast cells and eosinophils was measured prospectively from effusion of 33 randomly selected patients and 5 control subjects with chronic otitis media with effusion (OME). Atopy was determined by enzyme-linked immunosorbent assay. Middle ear biopsies from a second group of 8 OME patients and 4 controls were fixed in plastic and stained immunohistochemically for mast cells. RESULTS: Sixty-one percent of patients had extensive activation of mast cells in their middle ears. Among those with elevated tryptase in their effusion, 95.6% were atopic and 94.7% also had elevated levels of effusion eosinophilic cationic protein (ECP). Tryptase levels were elevated only in the effusion of atopic patients, as compared with 5 controls (P < .01). Mast cells were present in 6 of 8 OME ears and absent in all 4 normal ears. CONCLUSION: Mast cells and its mediator tryptase, both indicators of a Th2-driven immune response, are present in a majority of ears that have chronic effusion. These findings support the hypothesis that middle ear mucosa is capable of an allergic response and that the inflammation within the middle ear of most OME patients is allergic in nature.

Adolescent↗
PubMed1991

Ultrastructural and immunohistochemical characterization of normal mast cells at multiple body sites.

This article reviews the ultrastructural and immunohistochemical features of normal human mast cells (MC) at multiple tissue sites. Current literature indicates that granules containing discrete scrolls (scroll-rich morphology) are frequent in MC from bowel mucosa and lung, locations where the majority of MC show only tryptase immunoreactivity (MC(T)). In contrast, most MC from skin, breast parenchyma, axillary lymph nodes, and bowel submucosa are characterized by scroll-poor morphology (that is, granules are rimmed by incomplete scrolls forming parallel lamellae and containing central, amorphous granular material or grating/lattice-like structures) and show both tryptase and chymase immunoreactivity (MC(TC)). MC having granules with both scroll-rich and scroll-poor features can occur in all tissue sites, and an occasional MC, especially in lung and bowel, may show only chymase immunoreactivity (MC(C)). Chymase immunoreactivity in MC also is closely associated with avidin binding and carboxypeptidase reactivity. We conclude that there is ultrastructural and immunophenotypic diversity among normal human MC, although certain forms predominate in specific tissue environments. In skin, breast tissue, axillary lymph nodes, and bowel submucosa MC tend to have scroll-poor granules and stain for avidin, chymase, tryptase, and carboxypeptidase, whereas, in lung and bowel mucosa MC granules tend to be scroll-rich and stain only for tryptase with currently available reagents.

Avidin↗
PubMed2004

The production of collagen and the activity of mast-cell chymase increase in human skin after irradiation therapy.

Fibrosis is a common complication of radiotherapy. The pathogenesis of radiation-induced fibrosis is not known in detail. There is increasing evidence to suggest that mast cells contribute to various fibrotic conditions. Several mast-cell mediators have been proposed to have a role in fibrogenesis. Tryptase and chymase, the predominant proteins in mast cells, have been shown to induce fibroblast proliferation and collagen synthesis in vitro. In order to explore the role of mast cells in irradiation-induced fibrosis, we analyzed skin biopsies and suction blister fluid (SBF) samples from the lesional and healthy-looking skin of 10 patients who had been treated for breast cancer with surgery and radiotherapy. The biopsies were analyzed histochemically for mast-cell tryptase, chymase, kit receptor, and tumor necrosis factor-alpha. Skin collagen synthesis was assessed by determining the levels of type I and III procollagen amino-terminal propeptides (PINP and PIIINP) in SBF and using immunohistochemical staining for PINP. Immunohistochemical stainings for prolyl-4-hydroxylase reflecting collagen synthesis and chymase immunoreactivity in irradiated and control skin were also performed. The mean level of procollagen propeptides in SBF, which reflects actual skin collagen synthesis in vivo, was markedly increased in irradiated skin compared to corresponding healthy control skin areas. The mean number of PINP-positive fibroblasts was also significantly increased in the upper dermis of radiotherapy-treated skin. The number of cells positive for tryptase, chymase and kit receptor was markedly increased in irradiated skin. In addition, using double-staining techniques, it was possible to demonstrate that in some areas of the dermis, tryptase-positive mast cells and fibroblasts are closely associated. These findings suggest a possible role of mast cells in enhanced skin collagen synthesis and fibrosis induced by radiotherapy.

Adult↗
PubMed2005

Effect of salbutamol on nasal symptoms and mast cell degranulation induced by adenosine 5' monophosphate nasal challenge.

BACKGROUND: In addition to its well-known functional agonism at the level of beta(2) adrenergic receptors on airways smooth muscle cells, salbutamol appears to have additional protective effects, possibly through an inhibition of mast cell activation. OBJECTIVE: The aim of this study is to provide the first evidence in vivo of inhibition of human mast cell activation by salbutamol. METHODS: Nine atopic subjects received placebo and salbutamol (5 mg/mL) 15 min before an adenosine 5' monophosphate (AMP) nasal provocation in a double-blind crossover study design. The nasal lavage was collected from these subjects prior to or 3, 5, 15 or 30 min after the AMP nasal challenge, and concentrations of histamine and tryptase in the nasal lavage were measured. RESULTS: AMP nasal provocation produced considerable sneezing and induced a transient increase in histamine and tryptase release with peak values achieved at 3 min after the challenge in all the subjects studied. Compared with placebo, salbutamol significantly attenuated the release of histamine and tryptase induced by AMP challenge (P=0.048 and 0.020, respectively). Moreover, the AMP-induced sneezing was also inhibited by pre-treatment with salbutamol (P=0.004). CONCLUSIONS: Intranasal salbutamol attenuates nasal symptoms and inhibits histamine and tryptase release caused by AMP nasal provocation thus supporting the hypothesis that salbutamol may play an additional protective role in the airways by inhibiting mast cell activation.

Adenosine Monophosphate↗
PubMed2005

Mast cells and c-Kit expression in liver allograft rejection.

AIMS: The pathogenesis of rejection following liver transplantation is not fully understood. It has been postulated that mast cells may play a role in acute and chronic rejection of a number of other solid organ grafts. The aim of this study was to assess the possible role of mast cells and c-Kit+ cells in acute and chronic liver allograft rejection. METHODS AND RESULTS: Biopsy specimens from (i) 'time zero' grafts with a minimal degree of perfusion injury (controls), (ii) transplanted livers with different grades of acute rejection, and (iii) transplanted livers with end-stage chronic rejection, were stained immunohistochemically using monoclonal anti-mast cell tryptase and polyclonal anti-c-Kit antibodies. Tryptase- and c-Kit-positive cell densities were assessed by image analysis. Tryptase-positive mast cell densities (P<0.001) were strongly correlated with acute liver allograft rejection grades and chronic liver allograft rejection. Furthermore, a similarly strong relationship was found between c-Kit+ cell densities and increasing rejection grade (P<0.001). CONCLUSIONS: Tryptase- and c-Kit-positive mast cells form part of the inflammatory infiltrate in both acute and chronic liver allograft rejection, and may be important effector cells in these processes.

Graft Rejection↗
PubMed1995

Antiallergic actions of high topical doses of terbutaline in human nasal airways.

It is debatable whether beta 2-receptor agonists produce antiallergic effects in human airways. This question has been addressed in the present study by examination of both mast-cell indices and the physiologic response to allergen challenge in human nasal airways. Twelve asymptomatic patients with seasonal allergic rhinitis were investigated outside the pollen season. Intranasal allergen provocation was carried out with diluent and three increasing doses of allergen. Topical terbutaline sulfate (1.0 mg) was given 5 min prior to each allergen challenge and nasal lavage was carried out 10 min after each challenge. The study design was double-blind, placebo-controlled, crossover, and randomized. The allergen challenge-induced mast-cell activation and the ensuing physiologic response of the airway tissue were investigated by measuring a mast-cell-derived mediator (tryptase) and plasma proteins (albumin and alpha 2-macroglobulin), respectively, in the lavage fluids. Allergen provocation produced dose-dependent increments of nasal symptoms and lavage fluid levels of tryptase, albumin and alpha 2-macroglobulin. Both nasal symptoms (P < 0.05) and lavage fluid levels of tryptase (P < 0.05), albumin (P < 0.05), and alpha 2-macroglobulin (P < 0.01) were reduced by pretreatment with topical terbutaline sulfate. We conclude that high doses of topical terbutaline may produce significant antiallergic effects in human airways by equally reducing both tryptase release and plasma exudation in the acute allergic reaction in human airways. Further studies are now warranted to determine whether microvascular antipermeability effects of beta 2-receptor stimulation contribute to the present observations.

Administration, Topical↗
PubMed2005

Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine.

Nasal polyp tissue which contains mast cells and eosinophils is similar to the inflamed airway mucosa in cellular composition and mediator content. This investigation assessed the effect of desloratadine (DL), on activation of cells in nasal polyp tissue. Polyps were obtained from 22 patients with chronic rhinosinusitis [nine aspirin acetylosalitic acid (ASA)-sensitive and 13 ASA-tolerant]. Polyp tissue was dispersed by digestion, and preincubated with DL and incubated with anti-immunoglobulin E (IgE) or calcium ionophore. LTC4, eosinophil cationic protein (ECP) and tryptase concentrations in supernatants were measured by immunoassays. Desloratadine (1, 10 and 50 microM) inhibited calcium ionophore-induced LTC4 release by a mean of 29%, 50% and 63% respectively, and anti-IgE-induced LTC4 release by a mean of 27%, 35% and 39% respectively. Calcium ionophore-induced tryptase release was inhibited 60% and 69% by 10 and 50 microM of DL, respectively, and anti-IgE-induced tryptase release was inhibited 33%, 47% and 66% for 1, 10 and 50 microM of DL. Desloratadine 10 microM and 50 microM inhibited ECP release by and 45% and 48% respectively. Polyp tissue from ASA-sensitive patients when compared with ASA-tolerant patients released at baseline significantly more ECP (medians 120.0 microg/ml, range: 69.0-182.0 vs 63.4 microg/ml, range: 3.7-172.0; P <0.05), but similar amounts of tryptase and LTC4. This study demonstrated that DL inhibits activation of both eosinophils and mast cells derived from a site of airway mucosal inflammation.

Adult↗
PubMed1999

Stromal mast cells and nerve fibers in various chronic liver diseases: relevance to hepatic fibrosis.

OBJECTIVE: Recently, mast cells have been postulated to play a role in fibrogenesis in primary biliary cirrhosis (PBC) and alcoholic liver disease (ALD). There are only a few reports on nerve fibers in normal and pathological human livers. METHODS: We simultaneously investigated mast cells and nerve fibers in the stroma by single and double immunostainings and by quantitative morphometry in six normal livers and in 178 liver biopsies of PBC (n = 49), autoimmune hepatitis (n = 12), chronic hepatitis B (n = 37), chronic hepatitis C (n = 41), and ALD (n = 39). RESULTS: The densities of tryptase-positive mast cells, chymase-positive mast cells, and S-100-positive nerve fibers in the stroma were significantly higher in these chronic liver diseases than in normal livers. There were no significant differences in their densities among these chronic liver diseases. The densities of tryptase- and chymase-positive mast cells correlated significantly with degree of fibrosis, and density of nerve fibers correlated roughly with degree of fibrosis. Double immunostainings showed that some mast cells were in close contact with nerve fibers, and that, in selected cases, the percentages of mast cells positive for only tryptase (MC(T)) and those positive for both tryptase and chymase (MC(TC)) were 26% and 74%, respectively. CONCLUSIONS: These results suggest that mast cells and nerve fibers are involved in fibrogenesis in chronic liver diseases, regardless of their etiologies, probably by secreting fibrogenic substances. Some mast cells are innervated, and this innervation may stimulate mast cells to secrete fibrogenic substances, leading to hepatic fibrosis.

Adult↗
PubMed1998

Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU).

Previous studies on the frequency of mast cells (MCs) in recurrent aphthous ulcers (RAU) have yielded conflicting results. Monoclonal antibodies specific for tryptase (AA1) and anti-IgE (polyclonal antibody) were used to identify density and distribution of MCs in an immunohistochemical study of RAU (n=15), induced oral traumatic ulcers (TUs) (n=9), and control clinically healthy oral mucosa (n=15). Results were quantified by means of a VIDAS image analyzer. In all sections studied, IgE-positive cells showed similar frequency and distribution to tryptase-positive MCs. In RAU lesions, numerous tryptase-positive MCs were found in the sub-epithelial lamina propria, but MC numbers in the epithelium were low and present only in some RAU biopsies. MCs were also more numerous in RAU-inflammatory infiltrates (118+/-31 cells/mm2) than those seen in TU-inflammatory infiltrates (75+/-18 cells/mm2, P<0.001). MC activation/degranulation, as judged by diffuse extracellular tryptase staining, was a common feature within RAU-inflammatory infiltrates and at RAU-inflammatory infiltrates-connective tissue interfaces, which were often associated with connective tissue disruption. MC counts in the RAU connective tissue, lateral to the inflammatory infiltrates, were significantly greater than in the connective tissue of TUs and of control biopsies (124+/-36 vs 73+/-13 vs 69+/-21 cells/mm2, respectively; P<0.001). Overall, MCs were significantly increased in aphthae (116+/-26 cells/mm2) compared with TU lesions (72+/-11 cells/mm2, P<0.001) and controls (71+/-16 cells/mm2, P<0.001). In conclusion, MC numbers are increased in a typical topographical pattern, and the local MCs show signs of activation/degranulation suggesting active involvement of this cell type in RAU pathogenesis.

Adult↗
PubMed1998

Reappraisal of the expression of mast cell proteases of Mongolian gerbils (Meriones unguiculatus).

Mast cell proteases in the tongue and jejunum of Mongolian gerbils (Meriones unguiculatus) were examined by enzyme-histochemical methods. Both trypsin-like (tryptase) and chymotrypsin-like (chymase) protease activities were demonstrated in mast cells in the tongue of fresh cryosections. When frozen sections of the tongue were post-fixed in various fixatives, those fixed in Carnoy's fluid showed strongest enzyme activities. Tryptase and chymase activities in paraffin sections of both tissues were well preserved when tissues were fixed in Carnoy's fluid at 4 degrees C for 15 min. However, enzyme activities in both tissues, especially in the tongue, were drastically reduced by longer fixation time and higher temperature. When Carnoy-fixed (4 degrees C for 15 min) paraffin sections were treated with heparinase I or chondroitinase ABC before enzyme-histochemical stainings for proteases, tryptase activities were lost entirely in the tongue and mostly in the jejunum by heparinase I digestion, and slightly in both organs by chondroitinase ABC digestion. In contrast, chymase activities at both sites were not influenced by these pretreatments. These results show that although mast cells in the tongue as well as in the jejunum of Mongolian gerbils contain both tryptase and chymase activities, their stability to fixations is variable among organs so that tissue fixation conditions are crucial for the preservation. At least some part of the stability of mast cell proteases is dependent on the proteoglycans present in mast cell granules.

Animals↗
PubMed1995

Distribution, activation and tryptase/chymase phenotype of mast cells in the rheumatoid lesion.

OBJECTIVE: To determine the distribution, activation, and tryptase/chymase phenotype of mast cells (MCs) in the rheumatoid lesion. METHODS: MC tryptase and chymase were studied by immunohistochemistry using monoclonal antibodies and examination by brightfield, interference, and fluorescent microscopy. Thirty four specimens of cartilage-pannus junction and 26 specimens of rheumatoid synovium, all derived from knee surgery, were examined. RESULTS: MCs were identified in all specimens examined, but their distribution and local concentrations varied, both within and between specimens. As a proportion of total synovial cells, there were more MCs in fibrous synovial tissues than in those with active inflammatory cell infiltrations; MCs usually showed a peripheral distribution around lymphocytic/mononuclear cell infiltrations. Most cartilage-pannus specimens demonstrated local concentrations of MCs at, or close to, sites of cartilage erosion, a significant proportion of which showed extracellular tryptase indicative of MC degranulation. MC degranulation was often associated with localised oedema and disruption of the stromal matrix. Two MC phenotypes were identified: one population contained tryptase alone (MCT) whilst another contained both tryptase and chymase (MCTC). The ratio MCT:MCTC approximated 8:1. CONCLUSIONS: This histological study demonstrated that local concentrations of MCs and their activation/degranulation are commonly observed in the rheumatoid lesion, and especially at sites of cartilage erosion. Such observations add weight to the concept that MCs contribute to the processes of inflammation, matrix degradation and tissue remodelling.

Aged↗
PubMed1998

Effects of induced mast cell activation on prostaglandin E and metalloproteinase production by rheumatoid synovial tissue in vitro.

OBJECTIVE: To determine whether induced mast cell activation/degranulation in rheumatoid synovial explants modulates the production of prostaglandin E (PGE2), and the matrix metalloproteinases (MMPs) collagenase 1, gelatinase A, and stromelysin 1. METHODS: Synovial explant cultures were treated either with rabbit IgG anti-human IgE as a mast cell (MC) secretagogue or with non-immune rabbit IgG as controls. After 20 hours conditioned medium was assayed for the release of MC tryptase, PGE2, collagenase 1, gelatinase A, and stromelysin 1 using radioimmunoassay, enzyme linked immunosorbent assay, western blot, and zymogram techniques; tissue explants were examined immunohistologically for the relative distributions of MC tryptase, collagenase 1, and stromelysin 1. RESULTS: Over a 20 hour incubation period the MC secretagogue treated explants showed a significant increase in the quantities of released tryptase and PGE2 compared with controls. By contrast, the three MMPs showed variable values between experiments in response to MC activation; no reproducible trend of either an increased or decreased production of each MMP over control values was evident. Each MMP initially appeared as an inactive precursor form; collagenase 1 and stromelysin 1 were more effectively processed to active forms in the MC activated cultures. Immunolocalisation studies of MC activated explants showed that areas of extracellular tryptase were commonly associated with the local production of both collagenase 1 and stromelysin 1. CONCLUSION: MC degranulation induced artificially in rheumatoid synovial explant cultures consistently resulted in an increased production of PGE2 but had variable effects on the quantification of released collagenase 1, gelatinase A, and stromelysin 1. Such observations support the concept that activated synovial MCs within their native environment stimulate the production of non-MC derived PGE2 and may contribute to the regulation and processing of specific MMPs; both aspects represent important components of the inflammatory and degradative processes of the rheumatoid lesion.

Arthritis, Rheumatoid↗
PubMed2001

Functional effects of protease-activated receptor-2 stimulation on human airway smooth muscle.

The protease-activated receptor (PAR)-2 is present on the smooth muscle and epithelium of human airways and can be activated by mast cell tryptase, trypsin, or the PAR-2 activating peptide (AP). Trypsin and the PAR-2 AP induced contractions in human isolated airways, and these contractions were potentiated in the presence of the cyclooxygenase (COX) inhibitor indomethacin. Trypsin also increased the contractions to histamine in airways from sensitized (allergic) patients but not from nonsensitized (nonallergic) patients. Tryptase purified from human lung, skin and lung recombinant beta-tryptases, trypsin, and the PAR-2 AP all increased DNA synthesis in human airway smooth muscle (HASM) cells. Activation of PAR-2 by tryptase, trypsin, and the PAR-2 AP did not induce PGE(2) release from HASM cells. Trypsin and the PAR-2 AP increased the levels of intracellular calcium in HASM cells, with desensitization evident after treatment with either agonist. In conclusion, activation of PAR-2 can induce contractions of human airways, potentiate contractions to histamine, and induce proliferation and therefore may contribute to airway diseases such as asthma.

Adult↗
PubMed2003

The nonionic radiocontrast medium iopromide does not release endothelin-1 or activate cardiac mast cells during coronary angiography.

BACKGROUND: High osmolal ionic radiocontrast media (RCM) cause vascular release of endothelin-1 (ET-1) and activate mast cells. Iomeprol, a nonionic RCM, has recently been reported not to activate cardiac mast cells. This coronary angiography study was performed to extend those findings using another nonionic RCM, iopromide, and to further determine whether iopromide causes release of ET-1. METHODS: Pulmonary artery plasma ET-1, histamine and serum tryptase were determined before and 30 min following angiography with iopromide in 11 subjects. ET-1, histamine and tryptase were measured using immunoassays. RESULTS: The concentrations of ET-1 (1.36 +/- 0.66 pg/ml), histamine (2.63 +/- 1.15 nM), and beta (<1 microg/l) as well as total tryptase (8.25 +/- 4.63 microg/l) in the preangiography samples were within the normal range. Following angiography, the concentrations of ET-1 (0.95 +/- 0.80 pg/ml), histamine (3.08 +/- 1.06 nM), and beta (<1 microg/l) and total tryptase (7.00 +/- 5.56 microg/l) were not significantly different. None of the subjects demonstrated a postangiography increase in mediator concentration. CONCLUSIONS: This study demonstrates the lack of release of ET-1 by iopromide. The lack of cardiac mast cell activation by iopromide is consistent with the report that iomeprol also does not activate cardiac mast cells.

Adult↗
PubMed2006

Cathepsin B activates human trypsinogen 1 but not proelastase 2 or procarboxypeptidase B.

BACKGROUND/AIMS: Activation of trypsinogen to trypsin is a crucial step in the development of acute pancreatitis. The cause of this activation is not known although suggested explanations include autoactivation, cathepsin B-mediated activation and activation by mast cell tryptase. The aim of this study was to investigate cathepsin B and tryptase activation of pancreatic zymogens. METHODS: Trypsinogen-1, proelastase, and procarboxypeptidase B were purified from human pancreatic juice. Human cathepsin B and betaI-tryptase are commercial products. Activation and degradation of zymogens were measured by activity towards specific substrates for trypsin and pancreatic elastase, ELISAs for procarboxypeptidase B and its activation peptide, and a radioimmunoassay for the trypsinogen activation peptide. RESULTS: Cathepsin B caused activation of trypsinogen-1 with a trypsin yield of about 30% of that produced by enterokinase. Proelastase and procarboxypeptidase B was not activated by cathepsin B. None of the zymogens were inactivated by cathepsin B. Neither monomeric nor tetrameric tryptase could activate any of the examined zymogens. CONCLUSION: Cathepsin B is a competent activator of trypsinogen-1, although not as efficient as enterokinase. If cathepsin B is to play a role in protease activation in acute pancreatitis, this most probably occurs by activation of trypsinogen.

Carboxypeptidase B↗