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 1,675 records · Page 93Linked to original sources
PubMed2006

The role of allergic rhinitis in nasal responses to sudden temperature changes.

BACKGROUND: Air conditioning-induced rhinitis in allergic individuals is a common epidemiologic finding, but its physiopathology is still controversial. The aim of this study was to describe and compare the effects of experimental air conditioning temperature changes on the nasal mucosa of individuals with persistent allergic rhinitis compared with a control group. METHODS: A case-control challenge study was performed in a laboratory of thermal comfort with experimental twin challenge chambers set at a 12 degrees C difference in temperature. A group of 32 patients with persistent allergic rhinitis and a group of 16 control subjects were exposed for 30 minutes, 3 times alternately in each chamber. Nasal symptom scores were recorded and nasal samples collected before, immediately after, and 24 and 48 hours after the challenge. RESULTS: The rhinitis group showed a higher symptom score, epithelial shedding, percentage of eosinophils, total inflammatory cells, leukotriene C(4), eosinophil cationic protein, albumin, and tryptase levels compared with controls. There was also a significant increase in symptom score, total cells recovered, percentage of eosinophils, epithelial shedding, albumin, myeloperoxidase, and soluble intercellular adhesion molecule 1 in both groups compared with baseline levels. CONCLUSION: Sudden temperature changes led to a more pronounced inflammatory nasal response in the rhinitis group with the recruitment and activation of eosinophils. CLINICAL IMPLICATIONS: Persistent allergic rhinitis is a risk factor for developing sudden temperature change-related rhinitis even in the absence of allergen exposure.

Adult↗
PubMed2005

Successful treatment of systemic mastocytosis with high-dose interferon-alfa: long-term follow-up of a case.

Daily treatment of systemic mastocytosis with high-dose interferon-alfa often is not tolerated because of clinical or hematologic side effects. We report successful treatment of a patient with systemic mastocytosis, who was positive for the D816V mutation, with interferon alfa-2b at 10 million units three times per week. During 5 years of treatment, bone marrow infiltration by mast cells decreased from 50 to < or =5%, and there was a decrease (urinary N-methylhistamine excretion, 75%; serum tryptase concentration, 98%) or normalization (serum calcitonin value, urinary prostaglandin F2alpha excretion) of mast cell mediators. Side effects included mild depression (untreated) and biochemical hypothyroidism easily managed with supplemental levothyroxine.

Adult↗
PubMed2003

Gastrointestinal functions of proteinase-activated receptors.

Proteinase-activated receptors (PARs) are a family of G-protein-coupled-seven-trans-membrane-domain receptors, consisting of four family members. PARs, especially PAR-1, a thrombin receptor, and PAR-2, a receptor for trypsin, tryptase and coagulation factors VIIa and Xa, are abundantly distributed throughout the gastrointestinal tract. PAR-2, but not other PARs, induces salivary and pancreatic exocrine secretion. Both PAR-2 and PAR-1 play protective roles in the gastric mucosa, modulating a variety of gastric functions. However, the mechanisms underlying the mucosal protection caused by PAR-2 and PAR-1 are entirely different. In the intestinal mucosa, PAR-2 appears to play a dual role, being pro- and anti-inflammatory. PAR-1, PAR-2 and also PAR-4 modulate the motility of the smooth muscle in the gastrointestinal tract including the esophageal muscularis mucosae, producing contraction and/or relaxation upon activation. Thus, PARs, especially PAR-1 and PAR-2, play extensive roles in modulating the gastrointestinal functions.

Animals↗
PubMed2006

A hypothesis regarding complement activation and amniotic fluid embolism.

Amniotic fluid embolism, a rare, sudden and often fatal illness of pregnancy may not be a true embolic event resulting from the physical obstruction of the pulmonary vasculature. The high degree of variability in symptoms, the lack of characteristic findings on radiological exam, the absence of a dose-response effect on symptoms, and the occasional occurrence of coagulopathies are not entirely consistent with a physical block to the circulation as the main mechanism of disease. Alternatively, it might be the result of complement activation initiated by fetal antigen leaking into the maternal circulation. This rare immune response may be initiated by a rare pathological antigen, or by common antigens presented uncommonly--in amount, timing, or frequency of entry into the maternal circulation. Some very early evidence in AFE patients supports this hypothesis but is not conclusive. Complement levels remain well within the normal range during uncomplicated parturition. A prior theory that AFE might be a result of maternal anaphylaxis to fetal antigen has much less evidence to support it. The disseminated intravascular coagulation often seen in this and other serious obstetrical illnesses may be a secondary result of complement activation rather than the direct introduction of pro-coagulants into the maternal circulation although the link between the complement and coagulation pathways, if any, remains poorly defined. Through currently available laboratory testing, both the complement hypothesis and the anaphylaxis mechanism are able to be assessed. Direct measurement of serum complement as well as serum tryptase and urinary histamine are readily obtained tests in community hospitals as well as tertiary care hospitals. If the hypothesis proves true, this investigation may be of profound importance to understanding immune tolerance. Rather, than asking why one pregnant woman in 20,000 develops a violent immune reaction to the fetus, a better question is why do not all pregnant women reject the fetus which is a large collection of foreign antigens?

Complement Activation↗
PubMed2006

Anaphylaxis to intrathecal diamorphine.

A 42-year-old male underwent a total hip arthroplasty under subarachnoid anaesthesia with intrathecal bupivacaine and diamorphine. Shortly after the start of surgery, he suffered an allergic reaction that, at first, was difficult to distinguish from the recognised side-effects of intrathecal diamorphine. Once the diagnosis was made, he was treated with adrenaline and made a full recovery. The serum concentration of mast cell tryptase approximately 1.5h after the onset of the adverse incident confirmed an anaphylactic reaction. Skin prick testing several weeks later identified diamorphine as the likely causative agent, a drug overlooked initially as a potential cause. We believe this is the first report of intrathecal diamorphine causing anaphylaxis.

Adult↗
PubMed2005

Immediate reactions to contrast media: mediator release and value of diagnostic testing.

Immediate reactions to iodinated contrast media (ICM) resembles anaphylaxis. The recent literature demonstrates that histamine is released in vivo, with a peak concentration correlating within the severity grade of the reaction. Mast cells participate in severe reactions, as shown by several authors through the release of tryptase. In patients with severe reactions, intradermal testing with immediate reading appear positive to the culprit ICM, confirming an immune mechanism. For further procedures, a strict avoidance of the culprit ICM must be observed. The injection of another ICM giving negative skin tests has proved safe in a few patients.

Contrast Media↗
PubMed2005

Mast cells and IgE-bearing cells in lungs of RAO-affected horses.

Recurrent airway obstruction (RAO) is a common condition in stabled horses characterised by small airway inflammation and obstruction following exposure of susceptible horses to mouldy hay and straw. The aim of the present study was to investigate whether lung tissue from horses with RAO contains higher numbers of IgE-protein positive (+) cells and mast cells compared to controls after mouldy hay challenge. Furthermore, mast cell subtypes in lung tissue were investigated. IgE+ cells were detected in most lung tissue samples but no significant differences between RAO-affected and control horses were found. In the wall of the bronchi and bronchioli of both RAO-affected and control horses, mainly chymase+ mast cells (MC(C)) were present (85% in the bronchial wall and 77% in the wall of the bronchioli), while 73% of the mast cells (MC) around blood vessels were tryptase+ mast cells (MC(T)). No double stained MCs were detected. RAO-affected horses had significantly more MC(C) than controls in the wall of the bronchi (median=7.6 and 1.7 cell/mm(2), respectively, P< or =0.05). They also showed a tendency for more MC(C) in the wall of the bronchioli than controls (median=21 and 2.9 cells/mm(2), respectively, P=0.07) but there were no differences in MC(T) numbers. The data suggest an involvement of MC(C) in the pathogenesis of RAO. Independently of the clinical diagnosis, there was a significant relationship between high MC(C) numbers in the bronchial wall and lung fibrosis, suggesting that these MC(C) may be involved in tissue remodelling. Furthermore, high MC(C) numbers were also associated with increased infiltration with lymphocytes and neutrophils.

Animal Feed↗
PubMed2005

Hematopoietic prostaglandin D2 synthase in the chicken Harderian gland.

The Harderian gland (HG), a sero-mucous secreting organ in the eye orbit, has long been recognized as immunologically important in chickens. During experimentation to characterize immune components of the gland, proteomics analysis revealed the presence of hematopoietic prostaglandin D synthase (H-PGDS). Extraction of total RNA followed by RT-PCR produced cDNA of 597 base pairs. DNA sequencing revealed nucleic acid and predicted amino acid sequences that were 99% aligned with the one published sequence for chicken H-PGDS of the spleen. Alignment with murine, rat, and human H-PGDS were 69, 69, and 66%, respectively. Ocular vaccination of chickens with a Newcastle Disease/Infectious Bronchitis vaccine (Mass.-Ark. Strain) induced an increase in H-PGDS expression determined by real-time PCR. Furthermore, immunohistochemistry of frozen HG sections showed positive stained cells for both H-PGDS and mast cell tryptase in the sub-epithelial cell layers of the HG ducts. Based on the potent vasoactive role of PGD(2), it appears that the chicken HG is a site of active mucosal immunity partially mediated by PGD(2) synthesized by H-PGDS in the gland.

Amino Acid Sequence↗
PubMed2005

Immune dysregulation in flea allergy dermatitis--a model for the immunopathogenesis of allergic dermatitis.

BACKGROUND: Flea allergy dermatitis (FAD) is a common skin disease in dogs and can be induced experimentally. It often coexists with other allergic conditions. So far no studies have investigated the quantitative production of cytokine mRNA in skin biopsies and peripheral blood mononuclear cells (PBMC) in flea allergic dogs. OBJECTIVE: The aim of our study was to improve the understanding of the immunopathogenesis of allergic dermatitis as a response to fleabites. MATERIAL AND METHODS: Allergic and non-allergic dogs were exposed to fleas. Before and after 4 days of flea exposure mRNA was isolated from biopsies and PBMC. Production of chymase, tryptase, IL-4, IL-5, IL-13, TNF-alpha and IFN-gamma mRNA was measured by real-time RT-PCR. The inflammatory infiltrate in the skin was scored semi-quantitatively. The number of eosinophils, mast cells (MC) and IgE+ cells/mm2 was evaluated to complete the picture. RESULTS: FAD was associated with a higher number of MC before flea exposure and with a significant increase of eosinophils after flea exposure as compared to non-allergic dogs. The number of IgE+ cells was higher in allergic dogs before and after flea exposure. In allergic dogs mRNA for most cytokines and proteases tested was higher before flea exposure than after flea exposure. After exposure to fleas an increased mRNA production was only observed in non-allergic dogs. In vitro stimulation with flea antigen resulted in a decreased expression of most cytokines in allergic dogs before flea exposure. In contrast, in PBMC, only increased levels of IL-4 and IL-5 mRNA were observed in allergic dogs before flea exposure. However, after flea exposure and additional stimulation with flea antigen the production of mRNA for all cytokines tested was significantly increased in allergic dogs. CONCLUSION: We demonstrated that the response in biopsies and PBMC is different and that FAD is associated with a TH2 response.

Animals↗
PubMed2005

Mast cell density, angiogenesis, blood clotting, and prognosis in women with advanced ovarian cancer.

OBJECTIVE: To determine clinical or biological associations between mast cell density, blood clotting, angiogenesis, and survival of patients with advanced ovarian cancer. METHODS: Tumor tissue sections were assessed for mast cell density by staining for mast cell tryptase, blood clotting by staining of thrombosed blood vessels, and angiogenesis by CD34 expression. Chi-square, Kaplan-Meier, and Cox proportional hazard statistical analyses were used. RESULTS: 44 women with stage III-IV ovarian cancers had tumor blocks available for immunohistochemical analysis. Higher mean vessel density (MVD) (>11 vessels/400x field) predicted for better survival than lower MVD (< or =11 vessels/400x field) (P = 0.004). Women whose tumors had low levels of peri-tumoral mast cell infiltration had a mean survival of 40.6 months compared to 50.6 months in those whose tumors had high levels (P = 0.47). Tumors with higher MVD and high peri-tumoral mast cell infiltration had a mean survival of 80.3 months compared to 37.8 months in those with low mast cell density or low MVD (P = 0.015). Patients with tumors showing a low degree of blood clotting had a mean survival of 45.5 compared to 45.1 months in those with tumors showing a high degree of blood clotting (P = 0.91). There was no significant association between angiogenesis and mast cell density (P = 0.123). In multivariate analysis, higher MVD remained as a significant prognostic factor for improved survival after adjusting for clotting and mast cell density. CONCLUSIONS: Our data suggest that peri-tumoral mast cell infiltration in tumors with high MVD predicts for improved survival in women with advanced epithelial ovarian cancer.

Adult↗
PubMed2002

Increased angiogenesis in the bone marrow of patients with systemic mastocytosis.

Recent data suggest that angiogenesis in the bone marrow (BM) is augmented and associated with growth of neoplastic cells in various hematological malignancies. Systemic mastocytosis (SM) is a neoplasm affecting multilineage and mast cell (MC)-committed hemopoietic progenitors. In the present study, we have assessed the BM microvessel density (MVD) by CD34 immunohistochemistry in 21 patients with SM, 5 with cutaneous mastocytosis (no BM infiltrates), and 5 control cases (normal BM). The median BM MVD was significantly higher in SM compared to cutaneous mastocytosis or controls (P < 0.05). In addition, a significant correlation (r = 0.74) between the BM MVD and grade of MC infiltration (percent tryptase(+) BM infiltrates) was found in SM. Moreover, the MVD was higher in MC infiltrates compared to the nonaffected adjacent marrow (P < 0.05). Immunohistochemical staining revealed expression of vascular endothelial growth factor in MC infiltrates. The notion that SM is associated with increased BM angiogenesis and vascular endothelial growth factor expression may have implications for the biology of disease and development of new treatment strategies.

Antigens, CD34↗
PubMed2003

Basal nitric oxide modulates vascular effects of a peptide activating protease-activated receptor 2.

OBJECTIVES: Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor proteolytically activated by trypsin, tryptase or factor Xa. Alternatively, PAR2 can be activated by synthetic peptides whose sequence mimics the tethered ligand exposed after receptor cleavage. It is known that PAR2 modulates vascular reactivity, both in vitro and in vivo. The present study was designed to investigate the role of basal nitric oxide and cyclic nucleotides, adenosine 3'5'cyclic monophosphate (cAMP) and guanosine 3'5' cyclic monophosphate (cGMP), in the vasorelaxation induced by a PAR2-activating peptide (PAR2-AP; SLIGRL-NH(2)) on rat aorta in vitro. METHODS: A concentration-response curve to PAR2-AP was performed on rat thoracic aorta with or without a functional endothelium, and the effect of inhibitors was evaluated. The effect of PAR2-AP (10(-7)-3 x 10(-5) M) on endothelium-denuded aorta was also evaluated after tissue incubation with sodium nitroprusside. RESULTS: PAR2-AP (10(-7)-3 x 10(-5) M) caused an endothelium-dependent relaxation abolished by N(omega)-nitro-L-arginine methyl ester, L-NAME, and by the guanylyl cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), but unaffected by geldanamycin. Vasorelaxant effect of PAR2-AP was only partially inhibited by the adenylyl cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536), and it was increased by tissue incubation with the phosphodiesterase inhibitor, rolipram. On tissue without endothelium, PAR2-AP did not cause vasorelaxation, up to a concentration of 10(-4) M. However, after tissue incubation with sodium nitroprusside (SNP, 3 x 10(-9) M), the vasorelaxant effect of PAR2-AP was restored. Following tissue incubation with PAR2-AP, cAMP levels were significantly increased compared to control values. CONCLUSIONS: Our results suggest that vasorelaxation induced by PAR2-AP is modulated by basal nitric oxide with an involvement of both cyclic nucleotides, cGMP and cAMP.

Adenine↗
PubMed2000

Chymase mediates mast cell-induced angiogenesis in hamster sponge granulomas.

We investigated the contribution of mast cell chymase in mast cell-dependent angiogenesis using the hamster sponge-implant model, where angiogenesis in the granulation tissue surrounding the subcutaneously implanted sponge was evaluated by measuring the hemoglobin content. Daily local injection of compound 48/80 (3-100 microg/site/day), a potent mast cell activator, induced formation of granulomas and angiogenesis in time- and dose-dependent manners. This angiogenic response was inhibited by chymase inhibitors including chymostatin (> or = 1 nmol/site/day), soybean trypsin inhibitor (SBTI; > or = 1.4 nmol/site/day) and lima bean trypsin inhibitor (LBTI; > or = 3.3 nmol/site/day), but not by a tryptase inhibitor like leupeptin (> or = 700 nmol/site/day). Although pyrilamine (> or = 2,580 nmol/site/day), a histamine H1 receptor antagonist, and protamine (300 microg/site/day) also inhibited angiogenesis, these effects were much less pronounced than those by chymase inhibitors. Furthermore, antigen-induced angiogenesis in hamsters pre-sensitized with ovalbumin was also inhibited by the chymase inhibitors by 60-70%. Our results suggest that chymase is a major mediator in mast cell-mediated angiogenesis.

Animals↗
PubMed2002

Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats.

The effects of carbazochrome sodium sulfonate (AC-17), a capillary stabilizer, on pulmonary edema and dysfunction induced by ioxaglate, an ionic radiographic contrast medium, were evaluated in rats. The pulmonary edema was evaluated by the extravasation of intravenously injected Evans blue into lung tissues, while pulmonary dysfunction was determined by monitoring blood gasses including pO(2). Ioxaglate (4 g I/kg, i.v.) caused a marked increase in vascular permeability and a decrease in arterial pO(2). AC-17 reversed the ioxaglate-induced vascular hyperpermeability in a dose-dependent manner. In addition, AC-17 (10 mg/kg) significantly inhibited the decrease in arterial pO(2). In isolated rat pulmonary mast cells, ioxaglate markedly enhanced the histamine release, which was not affected by AC-17. On the other hand, AC-17 did significantly blocked the hyperpermeability induced in cultured bovine endothelial cells by tryptase, thrombin and proteinase-activated receptor-2 agonist peptide (SLIGKV-NH(2)). These findings suggest that AC-17 blocks radiographic contrast medium-induced pulmonary dysfunction by maintaining the endothelial barrier function. Thus, the compound is potentially useful for the prophylaxis of contrast media-induced acute pulmonary adverse events during angiography.

Animals↗
PubMed1998

The induction of a prolonged increase in microvascular permeability by human mast cell chymase.

Chymase is a major constituent of the secretory granules of human mast cells, but little is known of the contribution of this serine proteinase in acute allergic reactions. We have purified chymase from human skin tissue, and have investigated its potential to induce microvascular leakage in vivo. Injection of chymase into the skin of guinea pigs provoked an increase in microvascular leakage within 20 min. Although skin reactions were smaller than those elicited with similar quantities of histamine at this time point, they were much longer-lived, and were still apparent 120 min following injection. Chymase induced microvascular leakage was reduced in the presence of soybean trypsin inhibitor, and abolished by heat inactivating the enzyme, indicating dependence on an intact catalytic site. Little evidence was found for synergistic interactions between chymase and either histamine or tryptase. Antihistamine pretreatment of animals did not reduce the magnitude of skin reactions to chymase suggesting that they were not mediated by histamine release. Chymase could contribute to increases in microvascular permeability following mast cell degranulation in allergic disease.

Animals↗
PubMed2000

Human mast cells take up and hydrolyze anandamide under the control of 5-lipoxygenase and do not express cannabinoid receptors.

Human mast cells (HMC-1) take up anandamide (arachidonoyl-ethanolamide, AEA) with a saturable process (K(m)=200+/-20 nM, V(max)=25+/-3 pmol min(-1) mg protein(-1)), enhanced two-fold over control by nitric oxide-donors. Internalized AEA was hydrolyzed by a fatty acid amide hydrolase (FAAH), whose activity became measurable only in the presence of 5-lipoxygenase, but not cyclooxygenase, inhibitors. FAAH (K(m)=5.0+/-0.5 microM, V(max)=160+/-15 pmol min(-1) mg protein(-1)) was competitively inhibited by palmitoylethanolamide. HMC-1 cells did not display a functional cannabinoid receptor on their surface and neither AEA nor palmitoylethanolamide affected tryptase release from these cells.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1997

Identification of potential activators of proteinase-activated receptor-2.

In order to identify physiological activators of proteinase-activated receptor-2 (PAR-2), a peptide chloromethane inhibitor (biotinyl-Ser-Lys-Gly-Arg-CH2Cl) based on the cleavage site for activation of PAR-2 was synthesised and tested with 12 trypsin-like serine proteinases. The second-order rate constant (ki/Ki) for the formation of the covalent proteinase-inhibitor complex varied by 2 x 10(5)-fold between the proteinases. Biotinyl-Ser-Lys-Gly-Arg-CH2Cl reacted very rapidly with trypsin, acrosin from sperm and tryptase from mast cells: the ki/Ki values with these proteinases were greater than 10(5) M(-1) x s(-1). Thus, the specificity of these proteinases matched the sequence of the activation site of PAR-2 and it can be concluded that these proteinases are potential physiological activators of PAR-2.

Animals↗
PubMed2002

Insights from gene arrays on the development and growth regulation of uterine leiomyomata.

OBJECTIVE: To use microarray analysis as an unbiased approach to identify genes involved in the induction and growth of uterine leiomyomata. DESIGN: Screen by arrays for up to 12,000 genes in leiomyoma (L) and control myometrium (M) from nine patients. SETTING: University research laboratories. PATIENT(S): Nine patients in the follicular and luteal phases of the menstrual cycle. INTERVENTION(S): mRNA from L and M was converted to biotin-labeled cRNA and hybridized to cDNA oligonucleotide sequences on the arrays. MAIN OUTCOME MEASURE(S): Greater than two-fold change in gene expression between leiomyoma and matched myometrium. RESULT(S): Prominent among the 67 genes overexpressed in L relative to M were dlk or Pref-1, doublecortin, JM27, ionotropic glutamate receptor subunit 2, apolipoprotein E3, IGF2, semaphorin F, myelin proteolipid protein, MEST, frizzled, CRABP II, stromelysin-3, and TGFbeta3. The genes dlk, IGF2, and MEST are paternally expressed imprinted genes, and the others are involved in tissue differentiation and growth. Prominent among the 78 genes down-regulated in L relative to M were alcohol dehydrogenases 1alpha-gamma, tryptase, dermatopontin, thrombospondin, coxsackievirus receptor, nur77, and c-kit. CONCLUSION(S): Arrays offer large-scale screening of mRNA expression, which will help us differentiate between the genes and metabolic pathways necessary for leiomyoma growth and those regulating myometrial contractions.

Adult↗