A5025223838- Mast cells and histamine
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Asthma and respiratory diseases
- Polyamine Metabolism and Applications
- Peptidase Inhibition and Analysis
- Food Allergy and Anaphylaxis Research
- Chemical Synthesis and Analysis
- Protease and Inhibitor Mechanisms
- Transplantation: Methods and Outcomes
- Click Chemistry and Applications
- Neuropeptides and Animal Physiology
- Blood Coagulation and Thrombosis Mechanisms
- Antimicrobial Peptides and Activities
- Receptor Mechanisms and Signaling
- Urticaria and Related Conditions
- Neonatal Respiratory Health Research
- melanin and skin pigmentation
- Allergic Rhinitis and Sensitization
- Cystic Fibrosis Research Advances
- Proteoglycans and glycosaminoglycans research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Eosinophilic Disorders and Syndromes
- Microbial infections and disease research
- Cellular transport and secretion
- Immune Cell Function and Interaction
University of California, San Francisco
2013-2023
San Francisco VA Medical Center
2010-2022
Public Library of Science
2017
Northern California Institute for Research and Education
2005-2015
Cardiovascular Institute Hospital
1996-2012
Immunovaccine (Canada)
2012
University of Virginia
2003
University of Ferrara
2001
Mayo Clinic
1993
St. Louis Children's Hospital
1993
Expression of HPV16 early region genes in basal keratinocytes transgenic mice elicits a multistage pathway to squamous carcinoma. We report that infiltration by mast cells and activation the matrix metalloproteinase MMP-9/gelatinase B coincides with angiogenic switch premalignant lesions. Mast infiltrate hyperplasias, dysplasias, invasive fronts carcinomas, but not core solid tumors, where they degranulate close apposition capillaries epithelial basement membranes, releasing...
Mast cells appear to promote fibroblast proliferation, presumably through secretion of growth factors, although the molecular mechanisms underlying this mitogenic potential have not been explained fully by known mast cell-derived mediators. We report here that tryptase, a trypsin-like serine proteinase cell secretory granules, is potent mitogen for fibroblasts in vitro. Nanomolar concentrations dog tryptase strongly stimulate thymidine incorporation Chinese hamster lung and Rat-1 increase...
To investigate the hypothesis that neutrophil proteases stimulate airway gland secretion, we studied effect of human cathepsin G and elastase on secretion 35S-labeled macromolecules from cultured bovine serous cells. Both stimulated in a concentration-dependent fashion with threshold greater than or equal to 10(-10) M. Elastase was more potent G, causing maximal secretory response 1,810 +/- 60% over baseline at 10(-8) The (1,810 70% 10(-7) M) similar elastase. These responses were 10-fold...
The peptides substance P (SP) and vasoactive intestinal peptide (VIP) released from peptidergic neurons have potent effects on gland secretion smooth muscle tone. Because mast cells release proteases during degranulation, are located in many of the same tissue microenvironments into which SP VIP released, we wished to examine whether cell proteases, by cleaving thus inactivating these peptides, could modulate their effects. We used active site-titrated preparations two major neutral...
Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that cleaved and activated by trypsin-like enzymes. PAR-2 highly expressed small intestinal enterocytes where it luminal trypsin. The location, mechanism of activation, biological functions in the colon, however, are unknown. We localized to muscularis externa rat colon immunofluorescence. Myocytes primary culture also PAR-2, assessed immunofluorescence RT-PCR. Trypsin, SLIGRL-NH2 (corresponding tethered ligand), mast...
Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned sequenced in their entirety. The deduced amino acid sequences reveal 30-amino prepropeptide followed by 245-amino catalytic domain. C-terminal undecapeptide of the preprosequence is identical dog appears to be part prosequence unique among serine proteases. differences three domains include loss consensus N-glycosylation site one cDNA, which may explain some heterogeneity size susceptibility...
Abstract: Proteinase‐activated receptor‐2 (PAR‐2) is a G‐protein coupled receptor. Tryptic proteases cleave PAR‐2 exposing tethered ligand (SLIGKV), which binds and activates the Although highy expressed by cultured keratinocytes an inflammatory mediator, its precise localization in normal inflamed human skin unknown, that activate have not been identified. We localized immunohistochemistry, examined expression RT‐PCR RNA blotting, investigated activation mast cell tryptase. was to...
We cloned and characterized the canine A<sub>3</sub> adenosine receptor (AR) examined AR-induced degranulation of BR line mastocytoma cells. Canine A<sub>3</sub>AR transcript is found predominantly in spleen, lung, liver, testes encodes a 314-amino acid heptahelical receptor.<sup>125</sup>I-<i>N</i><sup>6</sup>-Aminobenzyladenosine binds to two affinity states with<i>K</i><sub><i>D</i></sub> values 0.7 ± 0.1 16 0.8 nm, reflecting G protein-coupled -uncoupled receptors, respectively. Xanthine...
Several lines of evidence suggest a possible role for mast cell proteases in modulating the biologic effects neuropeptides. To explore potential such interactions human airway, we examined activity tryptase, major secretory protease lung cells, against several neuropeptides with proposed regulatory functions airway. Using highly purified tryptase obtained from extracts lung, determined sites and rates hydrolysis vasoactive intestinal peptide (VIP), histidine-methionine (PHM), calcitonin...
Dipeptidyl peptidase I (DPPI) is the sole activator <i>in vivo</i> of several granule-associated serine proteases cytotoxic lymphocytes. <i>In vitro</i>, DPPI also activates mast cell chymases and tryptases. To determine whether essential for their activation vivo</i>, we used enzyme histochemical immunohistochemical approaches solution-based activity assays to study these enzymes in tissues bone marrow-derived cells (BMMCs) from +/+ −/− mice. We find that contain normal amounts...
Supernatants obtained by degranulation of dog mastocytoma cells greatly increased the sensitivity and magnitude contractile response isolated bronchial smooth muscle to histamine. The enhanced was reversed completely H1-receptor antagonists prevented an inhibitor tryptase (a major protease released with histamine from secretory granules mast cells). potentiation histamine-induced contractions reproduced active in pure form. due combination purified were abolished Ca2+ channel blockers...
1. Proteases regulate cells by cleaving proteinase-activated receptors (PARs). Thrombin and trypsin cleave PAR-1 PAR-2 on neurons astrocytes of the brain to morphology, growth survival. We hypothesized that thrombin mast cell tryptase, which are generated released during trauma inflammation, enteric PAR-2. 2. detected immunoreactive in > 60 % from myenteric plexus guinea-pig small intestine primary culture. A large proportion expressed substance P, vasoactive intestinal peptide or nitric...
The proto-oncogene c-KIT encodes a growth factor receptor, KIT, with ligand-dependent tyrosine kinase activity that is expressed by several cell types including mast cells. juxtamembrane coding region mutations causing constitutive activation of KIT are capable transforming lines and have been identified in human line situ gastrointestinal stromal tumors, but not demonstrated neoplastic cells from any species. To determine whether occur the development neoplasms, we examined canine...
In prior work we showed that a metallogelatinase is secreted from dog mastocytoma cells and directly activated by exocytosed mast cell α-chymase. The current identifies the protease as canine homologue of progelatinase B (92-kDa gelatinase, MMP-9), determines sites cleaved α-chymase, explores regulation gelatinase expression in cells. To obtain cDNA encoding complete sequence B, 2.3-kilobase clone was isolated BR library. sequenced predicts 704-amino acid protein 80% identical to human B....
Summary Background Mast cell‐deficient Kit W / W‐v mice are an important resource for studying mast cell functions in vivo . However, because they compound heterozygotes a mixed genetic background and infertile, cannot be crossed easily with other mice. Objective To overcome this limitation, we explored the use of W‐sh biology Results These C57BL/6 background, fertile can bred directly genetically modified Ten‐week‐old profoundly cell‐deficient. No cells detected any major organ, including...
Abstract Submucosal glands are the major sources of airway secretions in most mammals. Mast cells abundant environment submucosal and rich secreted proteases. To investigate hypothesis that mast cell proteases stimulate gland secretion, we studied ability two granule proteases, chymase tryptase, to cause secretion 35S-labeled macromolecules from a line cultured bovine serous cells. tryptase were purified dog mastocytoma Chymase markedly stimulated concentration-dependent fashion with...