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PubMed2006

cDNA cloning and substrate specificity of equine tryptase, a possible mediator in equine heaves.

BACKGROUND: Mast cell mediators are believed to play a central role in inflammatory lung disorders such as human allergic and occupational asthma. Equine heaves is characterized by reversible neutrophilic airway inflammation and airway obstruction, primarily due to bronchospasm and mucus hypersecretion, following exposure of susceptible horses to organic stable dusts. As such, heaves shares many similarities with human occupational dust-induced asthma and therefore it is proposed that mast cells may also be implicated in the pathogenesis of heaves. Tryptase, a mast cell-specific proteinase, can be used as an indicator of biological mast cell activity. OBJECTIVE: The aim of this study was to determine the cDNA sequence of equine tryptase and to investigate its substrate specificity in order to rationalize its enzymatic activity. METHODS: RT-PCR cloning was used to sequence equine tryptase. Substrate specificity of equine tryptase was investigated using arginine and lysine containing substrates. RESULTS: The cDNA and deduced amino acid (Aa) sequences for equine tryptase shared strong identity with other tryptases. Unusually for a trypsin-like proteinase however, equine tryptase has alanine at residue 216, rather than glycine, which confers increased arginine substrate specificity in vitro and may restrict fibrinogenolysis in vivo. CONCLUSION: Cloning and sequencing of the mast cell proteinase equine tryptase will allow molecular probing of its expression in the lung of control and heaves-affected horses. Further work is warranted to determine the biological relevance of the unique alanine 216 substitution in the molecular sequence of the equine tryptase substrate-binding pocket.

Amino Acid Sequence↗
PubMed1996

Mast cell-derived tryptase in odontogenic cysts.

Inflammatory and developmental cysts of the jaws are relatively common bone destructive lesions in the human maxillofacial skeleton but their pathogenesis is still poorly understood. In this study the role of mast cells (MC), and mast cell tryptase in particular, was evaluated in the pathophysiology of bone resorption and jaw cyst formation in different types of cysts. The distribution of MC and the amount of tryptase in histological tissue sections were determined by immunohistochemistry using monoclonal antihuman tryptase antibodies and the results were quantitated by using an image analyzing system. The amount of tryptase was further studied by Western-blotting and measurement of trypsin-like activity from the neutral salt extracts obtained from different types of jaw cysts. In contrast to control tissue, high trypsin-like activities and abundant immunoreactive tryptase were observed in the extracts of all types of cysts studied (radicular, dentigerous and keratocyst). In tissue sections the highest amount of tryptase-positive staining was observed in radicular cysts (mean 6.2% of reference area) and the lowest amount in keratocysts (mean 2.1% of reference area, P < 0.01). MC were found to be located in inflammatory cell-rich tissue areas and just beneath the cyst epithelium. Importantly, MC located at the border of bone were observed to be degranulated, indicating high activity of MC and release of tryptase at the regions of early bone destruction. Based on previous findings addressing the role of mast cell tryptase in proteolytic cascades, and the known association of MC with osteoporosis, we suggest that mast cells and mast cell tryptase may contribute significantly to jaw cyst tissue remodelling during growth of a cyst, and to the destruction of the surrounding bone, resulting in jaw cyst expansion.

Adolescent↗
PubMed2005

Tryptase activates phosphatidylinositol 3-kinases proteolytically independently from proteinase-activated receptor-2 in cultured dog airway smooth muscle cells.

Mast cell tryptase is a potent mitogen for many cells in the airways and lung, but the cellular mechanisms for its growth stimulatory effects are poorly understood. Our major goal was to determine whether tryptase activates phosphatidylinositol 3-kinases (PI 3-kinases) in cultured dog tracheal smooth muscle cells to induce its mitogenic effects. After exposure to tryptase, cells were lysed. Immunocomplexes prepared from the lysates using an antibody to the p85 subunit of PI 3-kinase, but not using anti-phosphotyrosine antibodies, possessed increased capacity to phosphorylate inositol on its D3 hydroxyl group. Tryptase also increased phosphorylation of Akt, a downstream target of PI 3-kinases. This effect was abolished by one PI 3-kinase inhibitor, wortmannin, and attenuated by another, LY-294004, which also blocked tryptase's mitogenic effects. Treatment of tryptase with p-amidino phenylmethanesulfonyl fluoride, to abolish its proteolytic activity irreversibly, inhibited its stimulatory effects on Akt phosphorylation. Proteinase-activated receptor-2 (PAR-2)-activating peptides failed to increase Akt phosphorylation in cultured dog tracheal smooth muscle cells, but the PAR-2-activating peptides did induce brisk increases in Akt phosphorylation in Madin-Darby canine kidney cells. We concluded that tryptase activates PI 3-kinases in cultured dog tracheal smooth muscle cells to induce its potent mitogenic effects. These effects of tryptase on PI 3-kinases appear to occur via novel proteolytic mechanisms independent from PAR-2. Also, tryptase, although comparable in mitogenic potency to platelet-derived growth factor (PDGF), induces considerably less tyrosine phosphorylation on proteins than occur in response to PDGF.

Animals↗
PubMed2000

Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2.

Mast cells play a potentially important role in fibroproliferative diseases, releasing mediators including tryptase that are capable of stimulating fibroblast proliferation and procollagen synthesis. The mechanism by which tryptase stimulates fibroblast proliferation is unclear, although recent studies suggest it can activate protease-activated receptor (PAR)-2. We therefore investigated the role of PAR-2 in tryptase-induced proliferation of human fetal lung and adult lung parenchymal and airway fibroblasts and, for comparative purposes, adult dermal fibroblasts. Tryptase (0.7-70 mU/ml) induced concentration-dependent increases in proliferation of all fibroblasts studied. Antipain, bis(5-amidino-2-benzimidazolyl)methane, and benzamidine inhibited tryptase-induced fibroblast proliferation, demonstrating that proteolytic activity is required for the proliferative effects of tryptase. RT-PCR demonstrated the presence of PAR-2 mRNA, and immunohistochemical staining localized PAR-2 to the cell surface of lung fibroblasts. In addition, specific PAR-2 activating peptides, SLIGKV and SLIGRL, mimicked the proliferative effects of tryptase. In contrast, human dermal fibroblasts only weakly stained with the PAR-2 antibody, PAR-2 mRNA was almost undetectable, and fibroblasts did not respond to PAR-2 activating peptides. These results suggest that tryptase induces lung, but not dermal, fibroblast proliferation via activation of PAR-2 and are consistent with the hypothesis that the release of tryptase from activated mast cells may play an important role in the fibroproliferative response observed in asthma, chronic obstructive pulmonary disease, and patients with pulmonary fibrosis.

Adult↗
PubMed2001

Selected contribution: tryptase-induced PAR-2-mediated Ca(2+) signaling in human airway smooth muscle cells.

Tryptase, the major mast cell product, is considered to play an important role in airway inflammation and hyperresponsiveness. Tryptase produces different, sometimes opposite, effects on airway responsiveness (bronchoprotection and/or airway contraction). This study was designed to examine the effect of human lung tryptase and activation of protease-activated receptor (PAR)-2 by synthetic activated peptide (AP) SLIGKV-NH(2) on Ca(2+) signaling in human airway smooth muscle (HASM) cells. Immunocytochemistry revealed that PAR-2 was expressed by HASM cells. Tryptase (7.5--30 mU/ml) induced a concentration-dependent transient relative rise in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) that reached 207 +/- 32 nM (n = 10) measured by indo 1 spectrofluorometry. The protease inhibitors leupeptin or benzamidine (100 microM) abolished tryptase-induced [Ca(2+)](i) increase. Activation of PAR-2 by AP (1-100 microM) also induced a concentration-dependent transient rise in [Ca(2+)](i), whereas the reverse peptide produced no effect. There was a homologous desensitization of the [Ca(2+)](i) response on repeated stimulation with tryptase or AP. U-73122, a specific phospholipase C (PLC) antagonist, xestospongin, an inositol trisphosphate (IP(3))-receptor antagonist, or thapsigargin, a sarcoplamic Ca(2+)-ATPase inhibitor, abolished tryptase-induced [Ca(2+)](i) response, whereas Ca(2+) removal, in the additional presence of EGTA, had no effect. Calphostin C, a protein kinase C inhibitor, increased PAR-2 [Ca(2+)](i) response. Our results indicate that tryptase activates a [Ca(2+)](i) response, which appears as PAR-2 mediated in HASM cells. Signal transduction implicates the intracellular Ca(2+) store via PLC activation and thus via the IP(3) pathway. This study provides evidence that tryptase, which is increasingly recognized as an important mediator in airway inflammation and hyperresponsiveness, is also a potent direct agonist at the site of airway smooth muscle.

Acetylcholine↗
PubMed2002

Serum tryptase levels in patients with mastocytosis: correlation with mast cell burden and implication for defining the category of disease.

BACKGROUND: The serum tryptase level is used as a diagnostic marker in mastocytosis and is considered to reflect the burden of (neoplastic) mast cells (MC). METHODS: In the present study, serum tryptase levels were measured in patients with mastocytosis by fluoroenzyme immunoassay and compared with the extent of infiltration of the bone marrow (BM) by neoplastic MC, determined by tryptase immunohistochemistry. Sixteen patients with cutaneous mastocytosis (CM) and 43 patients with systemic mastocytosis (SM) were examined. RESULTS: In most patients with CM (defined by the absence of dense compact MC infiltrates in tryptase-stained BM sections), normal or near-normal serum tryptase levels (median 10 ng/ml, range 2-23 ng/ml) were measured. By contrast, in the vast majority of patients with SM, elevated serum tryptase levels (median 67 ng/ml) were found. In addition, there was a significant correlation between the grade of infiltration of the BM by neoplastic MC and tryptase levels in patients with SM (r = 0.8). Moreover, enzyme levels differed significantly among the groups of patients with different types of SM. The highest levels (>900 ng/ml) were detected in the patient with MC leukemia, 2 patients with slowly progressing SM and high MC burden (smoldering SM) and 1 patient with indolent SM. In contrast, in all 3 patients with isolated BM mastocytosis (no skin lesions and no signs of multiorgan involvement), serum tryptase levels were <20 ng/ml. CONCLUSIONS: In summary, our data suggest that the measurement of serum tryptase is a reliable noninvasive diagnostic approach to estimate the burden of MC in patients with mastocytosis and to distinguish between categories of disease.

Adolescent↗
PubMed2002

Mast cell tryptase degrades HDL and blocks its function as an acceptor of cellular cholesterol.

OBJECTIVE: In human atherosclerotic lesions, degranulated mast cells are found in the vicinity of macrophage foam cells. Mast cell granules contain tryptase, a tetrameric serine protease requiring glycosaminoglycans for stabilization. No endogenous inhibitors have been described for tryptase, and the physiological functions of the enzyme are poorly understood. Here, we investigated the effects of human tryptase on the integrity of high density lipoprotein (HDL)3 and on its ability to release cholesterol from cultured mouse macrophage foam cells. METHODS AND RESULTS: Incubation of HDL3 with tryptase led to degradation of its apolipoproteins. Tryptase predominantly degraded a quantitatively minor subfraction of HDL3 that is lipid poor, exhibits electrophoretic pre-beta mobility, and contains either apolipoprotein A-I or apolipoprotein A-IV as its sole apolipoprotein. Moreover, tryptase caused functional changes in HDL3 by destroying its ability to promote high-affinity efflux of cholesterol from macrophage foam cells, ie, the pre-beta-HDL-dependent component of the process. Human aortic proteoglycans increased the ability of tryptase to proteolyze HDL3, suggesting that the proteoglycan-rich extracellular matrix of the arterial intima provides an appropriate environment for the extracellular actions of tryptase. CONCLUSIONS: By depleting pre-beta-HDL, mast cell tryptase may impair the initial step of reverse cholesterol transport and will then favor cellular accumulation of cholesterol during atherogenesis.

Animals↗
PubMed2005

Tryptase increases proliferative activity of human conjunctival fibroblasts through protease-activated receptor-2.

PURPOSE: Tryptase that is released by mast cell degranulation has recently been thought to play a key role in wound healing in allergic bronchitis. Conjunctival fibroblasts secrete mediators and extracellular matrices that could exacerbate inflammation and papillary formation in allergic conjunctivitis. This study was conducted to investigate the effect of tryptase on the proliferation of conjunctival fibroblasts and studied whether this effect was mediated by protease-activated receptor (PAR)-2. METHODS: Conjunctival fibroblasts were cultured with or without tryptase (0.1 ng/mL to 1.0 microg/mL), and the proliferation rate was assessed after 48 hours. The effects of tryptase inhibitors (leupeptin, benzamidine) and a PAR-2 agonist (SLIGKV) were examined. The existence of PAR-2 mRNA and protein in conjunctival fibroblasts was examined by RT-PCR and Western blot analysis, respectively. The existence of PAR-2 in cultured conjunctival fibroblasts and conjunctival papillae from patients with vernal keratoconjunctivitis, as well as conjunctival tissue from normal subjects was examined by immunohistochemistry. RESULTS: Conjunctival fibroblast proliferation was upregulated by tryptase in a dose-dependent manner (P < 0.001). Leupeptin and benzamidine inhibited tryptase-induced fibroblast proliferation (P < 0.05), and SLIGKV mimicked tryptase's effect. PAR-2 mRNA and protein were detected in cultured conjunctival fibroblasts using RT-PCR and Western blot analysis. PAR-2 immunoreactivity in both the cultured conjunctival fibroblasts and in stromal cells in excised conjunctival tissues was observed. CONCLUSIONS: Tryptase increased conjunctival fibroblast proliferation and this response appeared to be mediated by PAR-2. Mast cells are the most likely source of tryptase in the conjunctiva and may play an important role in chronic exacerbations with conjunctival papillary formation in allergic conjunctivitis.

Benzamidines↗
PubMed2001

Detection of tryptase in cytoplasmic granules of basophils in patients with chronic myeloid leukemia and other myeloid neoplasms.

Tryptases are serine proteases primarily expressed in mast cells. Normal blood basophils express only trace amounts of the enzyme. However, recent immunohistochemical studies have raised the possibility that neoplastic basophils express significant amounts of tryptase. In this study, tryptase expression was analyzed in normal and neoplastic basophils by immunoelectron microscopy using antitryptase monoclonal antibody G3. Basophils were obtained from patients with chronic myeloid leukemia (CML), idiopathic myelofibrosis (IMF), and myelodysplastic syndrome (MDS), and from healthy donors. Tryptase-immunoreactive material was detected in cytoplasmic granules of basophils in CML, IMF, and MDS. By contrast, normal basophils did not contain significant amounts of tryptase by immunoelectron microscopy. As assessed by reverse transcription-polymerase chain reaction, neoplastic basophils contained messenger RNA (mRNA) for alpha-tryptase, but no beta-tryptase mRNA. In summary, these data provide evidence that neoplastic basophils in CML, IMF, and MDS can express detectable amounts of tryptase. Therefore, tryptase should not be regarded as specific for mast cells when neoplastic myeloid cells are analyzed.

Basophils↗
PubMed1994

Sendai virus infection changes the subcellular localization of tryptase Clara in rat bronchiolar epithelial cells.

Tryptase Clara activates the infectivity of Sendai and influenza viruses proteolytically. In this study, we investigated changes in the subcellular localization of tryptase Clara in rat bronchioles with progression of Sendai virus infection. Tryptase Clara and Sendai virus F2 antigen were localized by light and electron immunohistochemical studies. In the uninfected rat lung, tryptase Clara was specifically localized in the secretory granules of respiratory bronchiolar epithelial nonciliated cells, but not in bronchiolar ciliated, or alveolar cells. In the initial stage of Sendai virus infection with slight pathological changes, however, anti-tryptase Clara was highly reactive in luminal peripheral membranes of both nonciliated and ciliated epithelial cells of the bronchioles together with some Sendai virus envelope glycoprotein, F2 antigen. In the progressed stage, tryptase Clara was hard to detect, with heavy accumulation of F2 antigen in the epithelial cells. These immunohistochemical results support our previous findings that in the bronchial lavage fluid tryptase Clara is significantly increased both in amount and activity after viral infection. These results suggest that Sendai virus stimulates the secretion of tryptase Clara from nonciliated bronchiolar epithelial cells to the airway lumen. Accumulation of tryptase Clara on the luminal surface of the bronchiolar epithelial cells and/or in the airway lumen may produce favourable conditions for proteolytic viral activation and multiplication.

Animals↗
PubMed1997

Mast cell tryptase potentiates histamine-induced contraction in human sensitized bronchus.

The mast cell plays a pivotal role in the early asthmatic response via release of mediators, which directly influence airway smooth muscle tone. Canine mast cell tryptase has been reported to potentiate the contractile response of canine isolated airways to histamine. The aim of this study was to investigate whether human mast cell tryptase potentiated contractile responses in human isolated bronchi. The effect of tryptase differed according to the sensitization status of the bronchi. In lung tissue from sensitized patients (those whose bronchial tissue contracted in response to the application of any of four common antigens) 90 ng.mL-1 of human purified lung tryptase markedly potentiated the contractile response to histamine. The maximal response as a percentage of maximal contraction to acetylcholine was 80 +/- 8% in control tissues and 119 +/- 6% in tryptase treated tissues (n = 4; p < 0.05). Tryptase, at a dose of 200 ng.mL-1, also potentiated responses but to a lesser degree, 100 +/- 5% (n = 4; p < 0.05). In nonsensitized bronchi, neither 90 nor 200 ng.mL-1 tryptase had any significant effect on histamine responses. The increased response in the presence of tryptase in sensitized tissue was inhibited by the calcium voltage-dependent channel antagonist, verapamil (10(-6) M). We have shown, for the first time, that human mast cell tryptase potentiates contraction in sensitized bronchi via a calcium-related mechanism. These findings provide a link between a mast cell derived product and in vitro human airway hyperresponsiveness.

Acetylcholine↗
PubMed2001

Role of mast cell tryptase in renal interstitial fibrosis.

Renal interstitial fibrosis is characterized by increased proliferation of fibroblasts and excessive accumulation of extracellular matrix. Mast cell tryptase has been implicated in the development of tissue fibrosis in skin and lungs. However, the significance of mast cell tryptase in human renal diseases has not been investigated. The potential role of mast cell-derived tryptase in the development of renal fibrosis was studied using immunohistochemical techniques and cultured human renal fibroblast cell lines. Semiquantitative immunostaining analysis of samples from 70 patients with several renal diseases, including IgA glomerulonephritis (GN) (n = 30), non-IgA GN (n = 5), membranous GN (n = 5), focal segmental glomerulosclerosis (n = 4), minor glomerular abnormalities (n = 5), lupus nephritis (n = 3), and acute or chronic tubulointerstitial nephritis (n = 18), revealed that the degree of renal interstitial fibrosis was well correlated with the number of infiltrating tryptase-positive mast cells (P < 0.01). Mast cells could not be detected in damaged glomeruli in any form of renal disease. [(3)H]Thymidine uptake experiments demonstrated that DNA synthesis by cultured renal fibroblasts was increased with the concentration of tryptase (0.5 to 5 nM) coincubated with heparin and was suppressed by coincubation with the protease inhibitors leupeptin and benzamidine hydrochloride. Tryptase alone also increased DNA synthesis by fibroblasts but exhibited less effectiveness, compared with the combination of tryptase and heparin. Conversely, heparin alone suppressed DNA synthesis by fibroblasts. Metabolic [(35)S]methionine-labeling experiments with cultured renal fibroblasts indicated that tryptase increased the synthesis of fibronectin and collagen type I, in a dose-dependent manner. These findings suggest that mast cell tryptase plays a role in the proliferation and extracellular matrix protein production of renal interstitial fibroblasts and thus contributes to the development of renal interstitial fibrosis.

Cell Division↗
PubMed2004

Modulation of tryptase secretion from human colon mast cells by histamine.

AIM: To investigate the ability of histamine to modulate tryptase release from human colon mast cells and the potential mechanisms. METHODS: Enzymatically dispersed cells from human colons were challenged with histamine, anti-IgE or calcium ionophore A23187 (CI), and the cell supernatants after challenge were collected. Tryptase release was determined with a sandwich ELISA procedure. RESULTS: Histamine at concentrations from 1 ng/mL was able to induce a "bell" shape dose related release of tryptase from colon mast cells. The maximum release of tryptase was approximately 3.5 fold more than spontaneous release. As little as 10 ng/mL histamine showed a similar potency to 10 microg/mL anti-IgE in induction of tryptase release. Histamine induced release of tryptase initiated at 10 s when histamine (100 ng/mL) was added to cells, gradually increased thereafter, and completed at 5 min. Both pertussis toxin or metabolic inhibitors were able to inhibit histamine induced tryptase release. When histamine and anti-IgE were added to colon mast cells at the same time, the quantity of tryptase released was similar to that induced by anti-IgE alone. The similar results were observed with CI. However, when various concentrations of histamine were incubated with cells for 20 min before adding anti-IgE or CI, the quantity of tryptase released was similar to that was induced by histamine alone. CONCLUSION: Histamine is a potent activator of human colon mast cells, which represents a novel and pivotal self-amplification mechanism of mast cell degranulation.

Colectomy↗
PubMed2006

Mast cell beta-tryptase selectively cleaves eotaxin and RANTES and abrogates their eosinophil chemotactic activities.

Recent studies have shown that a lack of eosinophils in asthmatic airway smooth muscle (ASM) bundles in contrast to the large number of mast cells is a key feature of asthma. We hypothesized that this is caused by beta-tryptase, the predominant mast cell-specific protease, abrogating the eosinophil chemotactic activities of ASM cell-derived eosinophil chemoattractants such as eotaxin and RANTES. We studied the effect of beta-tryptase on the immunoreactivities of human ASM cell-derived and recombinant eotaxin and other recombinant chemokines that are known to be produced by human ASM cells. We report in this study that purified beta-tryptase markedly reduced the immunoreactivity of human ASM cell-derived and recombinant eotaxin, but had no effect on eotaxin mRNA expression. The effect was mimicked by recombinant human beta-tryptase in the presence of heparin and was reversed by heat inactivation and the protease inhibitor leupeptin, suggesting that the proteolytic activity of tryptase is required. beta-Tryptase also exerted similar effects on recombinant RANTES, but not on the other chemokines and cytokines that were screened. Furthermore, a chemotaxis assay revealed that recombinant eotaxin and RANTES induced eosinophil migration concentration-dependently, which was abrogated by pretreatment of these chemokines with beta-tryptase. Another mast cell protease chymase also markedly reduced the immunoreactivity of eotaxin, but had no effect on RANTES and other chemokines and did not affect the influence of beta-tryptase on RANTES. These findings suggest that mast cell beta-tryptase selectively cleaves ASM-derived eotaxin and RANTES and abrogates their chemotactic activities, thus providing an explanation for the eosinophil paucity in asthmatic ASM bundles.

Asthma↗
PubMedDate not supplied

Serum tryptase in allergic rhinitis: effect of cetirizine and fluticasone propionate treatment.

PURPOSE: A specific reaction against several kinds of inhalant allergens characterizes allergic rhinitis. Mast cells play a crucial role in the allergic inflammation releasing histamine and other mediators. Tryptase is considered to be a specific marker of mast cell activation. This study was devoted to evaluate the serum tryptase in allergic rhinitis and to evaluate the effect of cetirizine and fluticasone propionate on mast cell activation. 13 subjects, suffering from perennial allergic rhinitis induced by Dermatophagoides pteronyssinus, were studied. MATERIALS AND METHODS: Tryptase serum levels were detected by the fluoroenzymeimmunoassay (Pharmacia & Upjohn AB, Uppsala, Sweden). Blood samples were taken four times: before starting the study, after two weeks of 10 mg cetirizine treatment once a day, after two weeks of wash-out, and again after 15 days of 100 micrograms intranasal fluticasone propionate therapy twice a day. RESULTS: In allergic rhinitis, the basal values of serum tryptase (M +/- SD: 6.1 +/- 2.4 micrograms/l) were significantly higher than in controls (M +/- SD: 3.0 +/- 1.2 micrograms/l). After the antihistamine treatment, tryptase values (M +/- SD: 4.4 +/- 1.8 micrograms/l) decreased significantly (p < 0.001). After the stop of antihistamine treatment, tryptase levels increased (M +/- SD: 5.5 +/- 2.6 micrograms/l, p < 0.001). After the topical corticosteroid treatment, tryptase values decreased again significantly (M +/- SD: 4.5 +/- 3.1 micrograms/l, p < 0.04). CONCLUSIONS: All these data seem to confirm the effective action of cetirizine and fluticasone propionate on tryptase serum levels. While the action of corticosteroid is well known, the action of cetirizine is still to define, considering the recent reports on anti-inflammatory effect of the second generation of H1 receptor antagonists. Further studies are necessary to understand if the pharmacological effect on tryptase is a specific one of cetirizine, or if it is common to other anti-H1 molecules.

Administration, Topical↗
PubMedDate not supplied

Modulation of tryptase release from human tonsil mast cells by protease inhibitors.

AIM: To examine the influence of protease inhibitors on tryptase release, and as a comparison the influence of the inhibitors on histamine secretion was assessed. METHODS: Enzymatically dispersed cells from human tonsil were challenged with anti-IgE or calcium ionophore A23187 (CI) in the absence or presence of the tryptase and chymase inhibitors, and tryptase and histamine release was determined. RESULTS: IgE-dependent tryptase release from dispersed tonsil mast cells was inhibited by a maximum of approximately 35.5% and 35.7% by N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) and N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK), respectively. The similar degree of inhibition of CI-induced tryptase release was observed also with these two inhibitors. Preincubation of TLCK or TPCK with cells at 37 degrees C for 20 min before addition of the stimulus improved slightly their ability to inhibit anti-IgE and CI-induced tryptase release. Protamine showed dual action on tryptase release from tonsil mast cells. The concentration-dependent inhibition of anti-IgE and CI-induced release of histamine from tonsil mast cells was also observed with TLCK, TPCK and protamine. The maximum inhibition of anti-IgE-induced histamine release was approximately 26.6%, 30.8% and 30.1% with TLCK, TPCK and protamine, respectively. At the concentrations tested, TLCK and TPCK by themselves did not stimulate tryptase and histamine release from tonsil mast cells. CONCLUSION: It was demonstrated that protease inhibitors were able to inhibit IgE-dependent tryptase release from human tonsil mast cells, which suggests strongly that they can be developed to a novel class of anti-inflammatory drugs to treat allergic conditions in man.

Antibodies, Anti-Idiotypic↗
PubMed2005

[Tryptase relation to VEGF in acute leukemia].

In order to investigate the role of tryptase in angiogenesis of acute leukemia (AL), the expressions of tryptase and vascular endothelial growth factor (VEGF) in leukemic cells from 61 patients with AL were examined by using immunocytochemical method, and the correlation between tryptase and VEGF was analyzed. The results showed that tryptase positive expression was found in 15 out of 51 patients with acute myeloid leukemia (AML) (M(1) 1/3, M(2) 7/15, M(3) 5/20, M(5) 2/8). Tryptase positive expression was 29.4% in AML. However, none of 10 patients with acute lymphocytic leukemia (ALL) showed tryptase expression. There were no correlations between the amounts of cells with tryptase expression and patient age, WBC count, numbers of blood or marrow myeloblasts and neutrophil POX. VEGF expression was revealed in 41 patients with AML (80.4%) and only 3 with ALL (30%). Significant correlation has been found between the expression of tryptase and that of VEGF in AML-M(2) (r = 0.65, P < 0.05). It is concluded that tryptase appears to be a myeloid-specific marker in AML and may be involved in the angiogenesis of AML-M(2).

Biomarkers, Tumor↗
PubMedDate not supplied

[Tryptase activity in colon mucosal samples of children with inflammatory bowel disease].

INTRODUCTION: mast cells are dispersed in many tissues, especially in the digestive and respiratory system mucosal membranes. Tryptase is the most important proteinase released from mast cells after degranulation. It influences strongly the cells and tissues by activating the inflammatory process. THE AIM OF THE STUDY: was to assess the activity of tryptase in colon mucosa samples in children with inflammatory bowel diseases (IBD) and in children with bleedings from lower part of gastrointestinal tract (GTB), without inflammation. MATERIAL AND METHODS: a group of 30 children with IBD was analyzed in the study. IBD is formed by three disease entities: ulcerative colitis (UC) - 14 patients, Crohn's disease (CD) - 9 patients and non-specific colitis (NSC) - 7 patients. Moreover, a group of 18 children with bleeding from lower part of gastrointestinal tract was studied. The activity of tryptase in homogenates of colon mucosal samples was estimated fluoroimmunoenzymatically. RESULTS: the results of our analysis showed no statistically important difference between the mean activity of tryptase in groups of children with IBD and GTB (31442 +/- 1304 vs 31868 +/- 775 ug/l). The study of tryptase activities in different disease entities of IBD group showed, that its value in ulcerative colitis group was 31382 +/- 1170 ug/l, in Crohn's disease group it was 31536 +/- 1120 ug/l; in non-specific colitis group the tryptase activity was 32277 +/- 498 ug/l. The analysis with Kruskal-Wallis Anova test revealed that the differences are statistically significant (p = 0.034). In post hoc test the outstanding value is the tryptase activity in children with NSC. Activity of tryptase in colon in much higher than its activity in plasma (normal range 1-19 ug/l). CONCLUSIONS: the activity of tryptase in mucosal membrane samples is much higher than in blood. The extent of mast cells degranulation may be dependent on the form of IBD.

Adolescent↗