Search

Background: Tryptase is used as a biomarker to support the diagnosis of anaphylaxis and hematologic diseases. In the event of a mast cell activation during anaphylaxis, a temporary increase in the concentration of tryptase may be seen. On the basis of clinical studies, an increase of 2 µg/L + 20% from basis level has been proposed as significant. To evaluate the increase in tryptase levels, the within-subject (CV I ) and between-subject (CV G ) biological variations should be known. This study was conducted to estimate the biological variation of tryptase and to identify the reference change value (RCV)., Methods: Blood samples were collected from healthy volunteers once a week consecutively over a 10-week period. Tryptase was measured by the use of a fluoroenzyme immunoassay (ImmunoCAP TM ; Thermo Fisher Scientific), and linear mixed-effects models were used to calculate the biological variation and RCV for both nontransformed and log-transformed tryptase., Results: Fourteen presumably healthy young adults (six males and eight females, age 23-35 years) were included. The CV I was 5.6% and the CV G was 31.5% (nontransformed data). Log-transformed data showed similar results. The analytical variation (CV A ) was 6.3% and the RCV was 23.5%., Conclusions: Young healthy adults without ongoing allergic reactions show low within-subject biological variation. Higher biological variation was observed between subjects., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Introduction: Mast cells are mostly known for their role in allergic reactions, as well as their involvement in diseases such as mast cell activation syndrome and systemic mastocytosis. One of the secreted enzymes during the allergic reaction and mast cell degranulation is tryptase. Recently, a new syndrome, namely - hereditary alpha tryptasemia, has been defined, originating from multiple copies of TPSAB1, the alpha-tryptase encoding gene. This syndrome has characteristic symptoms as well as biochemical and genetic markers. In this article we describe the first case of alpha tryptasemia diagnosed in Israel with emphasis on the typical symptoms and the biochemical and genetic workup needed to establish the diagnosis, as well as appropriate treatment.

Objective, Design: Mast cell tryptase (MCT) is elevated in arthritic joints, but its direct effects are not known. Here, we investigated MCT-evoked acute inflammatory and nociceptive mechanisms with behavioural, in vivo imaging and immunological techniques., Material and Subjects: Neurogenic inflammation involving capsaicin-sensitive afferents, transient receptor potential vanilloid 1 receptor (TRPV1), substance P (SP), neurokinin A (NKA) and their NK1 tachykinin receptor were studied using gene-deleted mice compared to C57Bl/6 wildtypes (n = 5-8/group)., Treatment: MCT was administered intraarticularly or topically (20 μl, 12 μg/ml). Capsaicin-sensitive afferents were defunctionalized with the TRPV1 agonist resiniferatoxin (RTX; 30-70-100 μg/kg s.c. pretreatment)., Methods: Knee diameter was measured with a caliper, synovial perfusion with laser Doppler imaging, mechanonociception with aesthesiometry and weight distribution with incapacitance tester over 6 h. Cytokines and neuropeptides were determined with immunoassays., Results: MCT induced synovial vasodilatation, oedema, impaired weight distribution and mechanical hyperalgesia, but cytokine or neuropeptide levels were not altered at the 6-h timepoint. Hyperaemia was reduced in RTX-treated and TRPV1-deleted animals, and oedema was absent in NK1-deficient mice. Hyperalgesia was decreased in SP/NKA- and NK1-deficient mice, weight bearing impairment in RTX-pretreated, TRPV1- and NK1-deficient animals., Conclusions: MCT evokes synovial hyperaemia, oedema, hyperalgesia and spontaneous pain. Capsaicin-sensitive afferents and TRPV1 receptors are essential for vasodilatation, while tachykinins mediate oedema and pain.

Objectives: To explore the value of mast cell tryptase and brain natriuretic peptide（BNP） in the differential diagnostic of sudden death due to hypersensitivity and coronary atherosclerotic heart disease., Methods: Totally 30 myocardial samples were collected from the autopsy cases in the Department of Forensic Pathology, Shanxi Medical University during 2010-2015. All samples were divided into three groups： death of craniocerebral injury group, sudden death of hypersensitivity group and sudden death of coronary atherosclerotic heart disease group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were detected by immunofluorescence staining and Western Blotting., Results: Immunofluorescence staining showed that the positive staining mast cell tryptase appeared in myocardium of sudden death of hypersensitivity group and coronary atherosclerotic heart disease group. Among the three groups, the expression of mast cell tryptase showed significantly differences through pairwise comparison （ P <0.05）; The expression level of BNP in sudden death of coronary atherosclerotic heart disease group were significantly higher than the sudden death of hypersensitivity group and death of craniocerebral injury group （ P <0.05）. The difference of the expression level of BNP between the sudden death of hypersensitivity group and the death of craniocerebral injury group had no statistical significance （ P >0.05）., Conclusions: The combined detection of the mast cell tryptase and BNP in myocardium is expected to provide help for the forensic differential diagnosis of sudden death due to hypersensitivity and coronary atherosclerotic heart disease., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine)

Background/aims: Previous studies have revealed that mast cells (MCs) may activate the protease-activated receptors and release of neuropeptides involved in the pathogenesis of irritable bowel syndrome (IBS). The levels of proteaseactivated receptor 2 (PAR-2) and tryptase can contribute to understanding the pathogenesis of IBS., Methods: Colonoscopic biopsies were performed of 38 subjects (20 with IBSdiarrhea [IBS-D], eight with IBS-constipation [IBS-C], and 10 healthy volunteers). The mRNA and protein levels of tryptase and PAR-2 were assessed by real-time PCR and Western blot. The levels of vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were measured by immunohistochemistry, and MCs were counted by toluidine blue staining., Results: Significant increases in the mRNA expression of tryptase (p<0.05, IBS-D, IBS-C vs control) and PAR-2 (p<0.05, IBS-D, IBS-C vs control) and in the tryptase protein level (p<0.05, IBS-D, IBS-C vs control) were detected in IBS. Elevations of MCs, CGRP, VIP and SP (p<0.05, IBS-D vs control) were observed for IBS-D only., Conclusions: Tryptase levels may upregulate the function of PAR- 2, resulting in the release of neuropeptide and they were correlated with clinical symptoms associated with IBS.

Aim: To investigate the relationship among histamine, tryptase and beta-hexosaminidase in the process of mast cell release and search for the suitable index to describe mast cell degranulation., Methods: Mast cell degranulation was performed in vitro, in which histamine, tryptase and beta-hexosaminidase are detected by spectrophotometry., Results: The concordance was found to exit among the three mediums, furthermore the study discloses that more similarity was found between tryptase and beta-hexosaminidase. Histamine was difficult and inconstant to be detected., Conclusion: Tryptase and beta-hexosaminidase are more suitable and accurately to reflect mast cell degranulation in vitro than histamine. Tryptase is the excellent index to detect mast cell degranulation in vitro.

An investigated flavonoid, quercetin, is reviewed in this article. Quercetin is a bioflavonoid found in red wine, grapefruit, onions, apples, black tea, and, in lesser amounts, in leafy green vegetables and beans. Quercetin has an antioxidant and anti-inflammatory activity and prevents cancer. Quercitin inhibits the growth of certain malignant cells in vitro, and histamine and most cyclin-dependent kinases and also displays unique anticancer properties. Quercetin is a natural compound that blocks substances involved in allergies and is able to act as an inhibitor of mast cell secretion, causes a decrease in the release of tryptase, MCP-1 and IL-6 and the down-regulation of histidine decarboxylase (HDC) mRNA from few mast cell lines. Quercetin is a safe, natural therapy that may be used as primary therapy or in conjunction with conventional methods.

Copyright of Best Practice Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

BACKGROUND: Hereditary alpha-tryptasemia (HαT) is characterized by elevated basal serum tryptase due to increased copies of the TPSAB1 gene. Individuals with HαT frequently present with multisystem complaints, including anaphylaxis and seemingly functional gastrointestinal (GI) symptoms. OBJECTIVE: We sought to determine the prevalence of HαT in an irritable bowel syndrome cohort and associated immunologic characteristics that may distinguish patients with HαT from patients without HαT. METHODS: Tryptase genotyping by droplet digital PCR, flow cytometry, cytometry by time-of-flight, immunohistochemistry, and other molecular biology techniques was used. RESULTS: HαT prevalence in a large irritable bowel syndrome cohort was 5% (N = 8/158). Immunophenotyping of HαT PBMCs (N ≥ 27) revealed increased total and class-switched memory B cells. In the small bowel, expansion of tissue mast cells with expression of CD203c, HLA-DR, and FcεRI, higher intestinal epithelial cell pyroptosis, and increased class-switched memory B cells were observed. IgG profiles in sera from individuals with HαT (N = 21) significantly differed from those in individuals with quiescent Crohn disease (N = 20) and non-HαT controls (N = 19), with increased antibodies directed against GI-associated proteins identified in individuals with HαT. CONCLUSIONS: Increased mast cell number and intestinal epithelial cell pyroptosis in the small intestine, and class-switched memory B cells in both the gut and peripheral blood associated with IgG reactive to GI-related proteins, distinguish HαT from functional GI disease. These innate and adaptive immunologic findings identified in association with HαT are suggestive of subclinical intestinal inflammation in symptomatic individuals.

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Eosinophilic esophagitis (EoE) is a type 2 helper T-cell (Th2)-mediated allergic disease that involves mast cells. This study aimed to clarify the relationship between perception of symptoms and mast cell levels in patients with EoE. Methods: We enrolled patients with asymptomatic esophageal eosinophilia (aEE) and those with symptomatic EoE. Immunofluorescence staining was performed on esophageal biopsy specimens to quantify mast cell-related molecules, such as tryptase, proteinase-activated receptor (PAR)-2, and vasoactive intestinal peptide receptor (VPAC)-1. Results: We evaluated 28 and 58 patients with aEE and EoE, respectively. There were no significant differences in clinical and endoscopic features and peak eosinophil counts between both groups. Mast cell tryptase-positive areas were significantly higher in EoE than in aEE (4.9 [3.5–6.2] vs. 2.0 [1.2–3.4] %, p < 0.01). The number of PAR-2-positive cells was significantly higher in EoE than in aEE (14 [8.8–20.0] vs. 4 [2.8–8.0] cells/high-power field [HPF], p < 0.01). The number of VPAC-1-positive cells was significantly higher in the EoE group than in the aEE group (13 [8.8–16.0] vs. 6 [3.0–9.3] cells/HPF, p < 0.01). A positive correlation was observed between the numbers of PAR-2-positive cells and VPAC-1-positive cells (r = 0.851, p < 0.01). Moreover, mast cell tryptase-positive areas positively correlated with the number of PAR-2- and VPAC-1-positive cells (r = 0.352, p < 0.01; r = 0.355, p < 0.01, respectively). Conclusions: Esophageal mast cells and their receptors, PAR-2 and VPAC-1, may contribute to the perception of symptoms in patients with EoE. [ABSTRACT FROM AUTHOR]

Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active β-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human β-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 Å crystal structure of a β-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma.

Tryptase test can be used as a clinical marker of mast cell activation. The present study is was aimed to identify variations in serum tryptase levels and their possible relationships with allergic reactions to protamine in low-risk patients undergoing cardiac bypass surgery. Thirty patients according to American Society of Anesthesiologists physical status III who underwent cardiac bypass surgery were enrolled. This prospective, non-randomised, clinical study was conducted in an operating room. Venous blood samples for tryptase measurements were obtained from cardiac bypass surgery patients upon admission to the operating room and immediately before and 30 min after the initiation of protamine administration. Signs of allergic reactions were recorded and management steps based on rapid effect response-based clinical assessments for diagnosis and treatment decisions during protamine administrations were described. Serum tryptase levels and clinical signs of allergic reactions, primarily mean arterial pressure (MAP), were recorded. Serum tryptase levels increased significantly and progressively during the bypass procedure (study power, 80%; sample size, 28; power of analysis, 99.8% with α=0.05); however, tryptase levels did not reach a sufficiently high level to confirm an allergic reaction. The MAP and heart rate decreased in 50% of the patients. Although tryptase increased significantly when compared with baseline levels, protamine-associated increases were not significant and failed to provide an unequivocal indication of an allergic response to protamine.

Abstract Objectives Biomarker levels in nasal secretions can reflect the inflammatory status of nasal mucosa and evolution of sinus disease. The aim of this study was to evaluate the relationship between local inflammatory mediator production and clinical characteristics of patients with nasal polyposis (NP). Methods Thirty‐one nonaeroallergen sensitized patients with NP (NANP), 29 aeroallergen sensitized patients with NP (ANP), and 30 subjects without inflammation of nasal mucosa as controls (C) entered this prospective, cross‐sectional study. Clinical parameters (symptoms, endoscopic, and radiological findings) were assessed. The concentrations of heat shock protein 70 (HSP70), eosinophil cationic protein (ECP), tryptase, substance P and Clara cell protein 16 (CC16) were measured in the nasal secretion samples of all participants by ELISA method. Results Our results showed higher concentrations of HSP70, ECP, and tryptase in ANP than in NANP and C (p

Purpose: Kaposi sarcoma (KS) is a vascular tumor initiated by infection of endothelial cells (ECs) with KS-associated herpesvirus (KSHV). KS is dependent on sustained proinflammatory signals provided by intralesional leukocytes and continued infection of new ECs. However, the sources of these cytokines and infectious virus within lesions are not fully understood. Here, mast cells (MCs) are identified as proinflammatory cells within KS lesions that are permissive for, and activated by, infection with KSHV.Experimental Design: Three validated MC lines were used to assess permissivity of MCs to infection with KSHV and to evaluate MCs activation following infection. Biopsies from 31 AIDS-KS cases and 11 AIDS controls were evaluated by IHC for the presence of MCs in KS lesions and assessment of MC activation state and infection with KSHV. Plasma samples from 26 AIDS-KS, 13 classic KS, and 13 healthy adults were evaluated for levels of MC granule contents tryptase and histamine.Results: In culture, MCs supported latent and lytic KSHV infection, and infection-induced MC degranulation. Within KS lesions, MCs were closely associated with spindle cells. Furthermore, MC activation was extensive within patients with KS, reflected by elevated circulating levels of tryptase and a histamine metabolite. One patient with clinical signs of extensive MC activation was treated with antagonists of MC proinflammatory mediators, which resulted in a rapid and durable regression of AIDS-KS lesions.Conclusions: Using complimentary in vitro and in vivo studies we identify MCs as a potential long-lived reservoir for KSHV and a source of proinflammatory mediators within the KS lesional microenvironment. In addition, we identify MC antagonists as a promising novel therapeutic approach for KS. Clin Cancer Res; 24(20); 5085-97. ©2018 AACR.

Tryptase test can be used as a clinical marker of mast cell activation. The present study is was aimed to identify variations in serum tryptase levels and their possible relationships with allergic reactions to protamine in low-risk patients undergoing cardiac bypass surgery. Thirty patients according to American Society of Anesthesiologists physical status III who underwent cardiac bypass surgery were enrolled. This prospective, non-randomised, clinical study was conducted in an operating room. Venous blood samples for tryptase measurements were obtained from cardiac bypass surgery patients upon admission to the operating room and immediately before and 30 min after the initiation of protamine administration. Signs of allergic reactions were recorded and management steps based on rapid effect response-based clinical assessments for diagnosis and treatment decisions during protamine administrations were described. Serum tryptase levels and clinical signs of allergic reactions, primarily mean arterial pressure (MAP), were recorded. Serum tryptase levels increased significantly and progressively during the bypass procedure (study power, 80%; sample size, 28; power of analysis, 99.8% with α=0.05); however, tryptase levels did not reach a sufficiently high level to confirm an allergic reaction. The MAP and heart rate decreased in 50% of the patients. Although tryptase increased significantly when compared with baseline levels, protamine-associated increases were not significant and failed to provide an unequivocal indication of an allergic response to protamine. [ABSTRACT FROM AUTHOR]

Objectives: Biomarker levels in nasal secretions can reflect the inflammatory status of nasal mucosa and evolution of sinus disease. The aim of this study was to evaluate the relationship between local inflammatory mediator production and clinical characteristics of patients with nasal polyposis (NP). Methods: Thirty‐one nonaeroallergen sensitized patients with NP (NANP), 29 aeroallergen sensitized patients with NP (ANP), and 30 subjects without inflammation of nasal mucosa as controls (C) entered this prospective, cross‐sectional study. Clinical parameters (symptoms, endoscopic, and radiological findings) were assessed. The concentrations of heat shock protein 70 (HSP70), eosinophil cationic protein (ECP), tryptase, substance P and Clara cell protein 16 (CC16) were measured in the nasal secretion samples of all participants by ELISA method. Results: Our results showed higher concentrations of HSP70, ECP, and tryptase in ANP than in NANP and C (p <.001 for all markers). On the other hand, levels of CC16 were significantly higher in C than in NANP and ANP groups (p <.001; p <.001, respectively). We found positive correlations between HSP70, ECP, tryptase, and substance P levels and nasal symptom score in patients with NP. Also, HSP70, ECP, tryptase, and substance P showed different levels of positive correlation among themselves, with HSP70 showing highest positive correlation with ECP. Finally, relatively strong negative correlations were found between the levels of CC16 and nasal symptoms, as well as between the CC16 levels and levels of other four mediators in nasal fluid. Conclusion: HSP70, ECP, tryptase, and substance P might play a role in the pathogenesis of NP. The results suggest that chronic inflammation in NP involves a self‐sustaining local release of HSP70, ECP, and tryptase, independent of aeroallergen stimulation of the mucosal layer, although the production of these mediators is higher in aeroallergen sensitized NP patients. [ABSTRACT FROM AUTHOR]

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.

Introduction: Food allergy is the major cause of pediatric anaphylaxis. Characteristics and triggers may be different in different geographical regions. Studies focusing on food-induced anaphylaxis (FIA) in Asian developing countries are limited. Our study aimed to study characteristics of FIA in a tertiary care center in an Asian developing country. Methods: Retrospective review of pediatric anaphylaxis admission and outpatient visit at a tertiary care hospital in Bangkok, Thailand during 2008–2018 was performed. Data regarding clinical presentation, place reaction occurred, time of onset, investigations (serum tryptase, specific immunoglobulin E, and skin test), treatment, and follow-up periods were collected. Results: One hundred seventy-four anaphylaxis admission records of which 61 episodes of FIA were retrieved. Data from outpatients visit consisted of 17 patients. Most patients were male (76.7%). The median age was 7.1 years (interquartile range 1.9–12.4). The major causes of FIA were shrimp/shellfish (37%), wheat (15.1%), and cow's milk (11%). Food causing anaphylaxis varied according to age-group: infants had anaphylactic reactions to egg, wheat, and cow's milk, preschools to wheat and peanut, and older children to shrimp/shellfish. Cutaneous manifestations occurred in all patients, followed by lower respiratory tract symptoms (83.6%) and gastrointestinal symptoms (50.8%). There was no biphasic anaphylaxis reported. Elevated serum tryptase was found in only 4 patients (7%). Conclusion: Recognizing characteristics of pediatric FIA is crucial. The common causes of FIA in our study in Asian children were egg in infants, wheat and peanut in preschool children, and shrimp/shellfish in school-age children and adolescents. Skin manifestation presented in all patients with FIA. [ABSTRACT FROM AUTHOR]

Tryptic serine proteases of bronchial epithelium regulate ion flux, barrier integrity, and allergic inflammation. Inhibition of some of these proteases is a strategy to improve mucociliary function in cystic fibrosis and asthmatic inflammation. Several inhibitors have been tested in pre-clinical animal models and humans. We hypothesized that these inhibitors inactivate a variety of airway protease targets, potentially with bystander effects. To establish relative potencies and modes of action, we compared inactivation of human prostasin, matriptase, airway trypsin-like protease (HAT), and β-tryptase by nafamostat, camostat, bis(5-amidino-2-benzimidazolyl)methane (BABIM), aprotinin, and benzamidine. Nafamostat achieved complete, nearly stoichiometric and very slowly reversible inhibition of matriptase and tryptase, but inhibited prostasin less potently and was weakest versus HAT. The IC50 of nafamostat's leaving group, 6-amidino-2-naphthol, was >104-fold higher than that of nafamostat itself, consistent with suicide rather than product inhibition as mechanisms of prolonged inactivation. Stoichiometric release of 6-amidino-2-naphthol allowed highly sensitive fluorometric estimation of active-site concentration in preparations of matriptase and tryptase. Camostat inactivated all enzymes but was less potent overall and weakest towards matriptase, which, however was strongly inhibited by BABIM. Aprotinin exhibited nearly stoichiometric inhibition of prostasin and matriptase, but was much weaker towards HAT and was completely ineffective versus tryptase. Benzamidine was universally weak. Thus, each inhibitor profile was distinct. Nafamostat, camostat and aprotinin markedly reduced tryptic activity on the apical surface of cystic fibrosis airway epithelial monolayers, suggesting prostasin as the major source of such activity and supporting strategies targeting prostasin for inactivation.

Rosacea is a chronic inflammatory skin disease whose pathophysiological mechanism is still unclear. However, it is known that mast cell (MC) numbers are increased in the dermis of rosacea patients. MC proteases not only recruit other immune cells, which amplify the inflammatory response, but also cause vasodilation and angiogenesis. MCs are also one of the primary sources of cathelicidin LL-37 (Cath LL-37), an antimicrobial peptide that has been shown to be an enabler of rosacea pathogenesis. Here, we demonstrate that MCs are key mediators of cathelicidin-initiated skin inflammation. After Cath LL-37 injection into the dermis, MC-deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (KitW-sh) mice did not develop rosacea-like features. Conversely, chymase (P