Research Topics
Genomes and Genes
| George H CaugheySummaryAffiliation: University of California Country: USA Publications
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Detail Information
Publications
Tryptase genetics and anaphylaxisGeorge H Caughey
Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco, CA 94121, USA
J Allergy Clin Immunol 117:1411-4. 2006..Thus pro- and mature beta tryptase measurements are useful but associated with false-negative and false-positive results, which need to be considered in drawing clinical conclusions in cases of suspected anaphylaxis...
Mast cell tryptases and chymases in inflammation and host defenseGeorge H Caughey
Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA
Immunol Rev 217:141-54. 2007..Thus, like mast cells themselves, mast cell serine peptidases play multiple roles in host defense, and any accounting of benefit versus harm is necessarily context specific...
Mast cell proteases as protective and inflammatory mediatorsGeorge H Caughey
Department of Medicine, University of California at San Francisco, San Francisco, Califonia, USA
Adv Exp Med Biol 716:212-34. 2011....
Guinea pig chymase is leucine-specific: a novel example of functional plasticity in the chymase/granzyme family of serine peptidasesGeorge H Caughey
Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
J Biol Chem 283:13943-51. 2008..These findings are evidence that chymase-like peptidase specificity is sensitive to small changes in structure and provide the first example of a vertebrate Leu-selective peptidase...
Neutrophil histamine contributes to inflammation in mycoplasma pneumoniaXiang Xu
Cardiovascular Research Institute, Department of Microbiology Immunology, University of California at San Francisco, and Veterans Affairs Medical Center, San Francisco 94121, USA
J Exp Med 203:2907-17. 2006..These findings suggest that neutrophils, provoked by mycoplasma, greatly expand their capacity to synthesize histamine, thereby contributing to lung and airway inflammation...
Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cellsShilpa Nimishakavi
Cardiovascular Research Institute, San Francisco, CA, USA
Am J Physiol Lung Cell Mol Physiol 303:L97-106. 2012..In conclusion, prostasin is present, mature and active on the apical surface of wild-type and CF bronchial epithelial cells, where it can be targeted for inhibition via the airway lumen...
Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage siteWilfred W Raymond
Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0911, USA
J Biol Chem 278:34517-24. 2003..8 nM) and 2,700- and 1,300-fold selective for chymase over cathepsin G and chymotrypsin, respectively. In summary, these findings reveal albumin to be a substrate for chymase and identify a potentially useful new chymase inhibitor...
Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosaXiang Xu
Department of Medicine, University of California at San Francisco, San Francisco, California, USA
J Leukoc Biol 91:275-84. 2012..These findings raise the possibility that Pseudomonas-stimulated neutrophils can enhance airway inflammation by producing histamine...
Mast cell alpha and beta tryptases changed rapidly during primate speciation and evolved from gamma-like transmembrane peptidases in ancestral vertebratesNeil N Trivedi
Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, CA 94143, USA
J Immunol 179:6072-9. 2007....
How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolutionWilfred W Raymond
Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA 94143, USA
J Immunol 185:5360-8. 2010....
Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell lineZhenyue Tong
Cardiovascular Research Institute, and Department of Medicine, University of California at San Francisco, San Francisco 94143, USA
Am J Physiol Lung Cell Mol Physiol 287:L928-35. 2004....
Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in miceRachel E Sutherland
Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
PLoS ONE 6:e27564. 2011....
Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthmaRyan H Dougherty
Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA
J Allergy Clin Immunol 125:1046-1053.e8. 2010..We also found that asthmatic subjects can be divided into 2 subgroups ("T(H)2 high" and "T(H)2 low" asthma) based on epithelial cell gene signatures for the activity of T(H)2 cytokines...
Mast cells protect mice from Mycoplasma pneumoniaXiang Xu
Pulmonary and Critical Care Medicine, Mailstop 111-D, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121
Am J Respir Crit Care Med 173:219-25. 2006..CONCLUSIONS: These findings suggest that mast cells are important for innate immune containment of and recovery from respiratory mycoplasma infection...
Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchorGeorge M Verghese
Department of Medicine, University of Virginia, Charlottesville, Virginia 22908 0546, USA
Am J Physiol Cell Physiol 291:C1258-70. 2006..These studies suggest that cell-specific Gpld1- or peptidase-dependent pathways for prostasin secretion may control prostasin functions in a tissue-specific manner...
Mast cell and neutrophil peptidases attack an inactivation segment in hepatocyte growth factor to generate NK4-like antagonistsWilfred W Raymond
Department of Medicine and Cardiovascular Research Institute, The University of California at San Francisco, San Francisco, California 94143, USA
J Biol Chem 281:1489-94. 2006..This work reveals a potential physiological pathway for inactivation of HGF and generation of NK4-like antagonists...
Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss-of-function mutationsNeil N Trivedi
Cardiovascular Research Institute, University of California at San Francisco, San Francisco, Calif, USA
J Allergy Clin Immunol 124:1099-105.e1-4. 2009..Tryptase gene loci TPSAB1 and TPSB2 are known to be polymorphic, but the nature and extent of diversity at these loci have not been fully explored...
Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and creates a reservoir of angiotensin II-generating activityWilfred W Raymond
Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA 94143, USA
J Immunol 182:5770-7. 2009....
Mastin is a gelatinolytic mast cell peptidase resembling a mini-proteasomeWilfred W Raymond
Department of Medicine, Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA 94143 0911, USA
Arch Biochem Biophys 435:311-22. 2005....
Protease-activated receptor 2, dipeptidyl peptidase I, and proteases mediate Clostridium difficile toxin A enteritisGraeme S Cottrell
Center for the Neurobiology of Digestive Disease, Department of Surgery, University of California, San Francisco, San Francisco, California 94143 0660, USA
Gastroenterology 132:2422-37. 2007..We studied the role of protease-activated receptor 2 (PAR(2)) and its activating enzymes, trypsins and tryptase, in Clostridium difficile toxin A (TxA)-induced enteritis...
Cathepsins L and S are not required for activation of dipeptidyl peptidase I (cathepsin C) in miceJon Mallen-St Clair
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0111, USA
Biol Chem 387:1143-6. 2006..These results show that neither cathepsin L nor S is required for activation of DPPI and suggest that one or more additional proteases is responsible...
Mast cell dipeptidyl peptidase I mediates survival from sepsisJon Mallen-St Clair
Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, California 94143 0911, USA
J Clin Invest 113:628-34. 2004..These results indicate that mast cell DPPI harms the septic host and that DPPI is a novel potential therapeutic target for treatment of sepsis...
The αvβ6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cellsKotaro Sugimoto
Lung Biology Center, Department of Medicine, UCSF, San Francisco, California, USA
J Clin Invest 122:748-58. 2012....
Chimerism, point mutation, and truncation dramatically transformed mast cell delta-tryptases during primate evolutionNeil N Trivedi
Cardiovascular Research Institute of the University of California at San Francisco, San Francisco, CA, USA
J Allergy Clin Immunol 121:1262-8. 2008..However, much of the ancestral MCP-7 ortholog was replaced by parts of other tryptases, creating chimeric delta-tryptase. Human delta-tryptase's limited activity is hypothesized to be due to truncation and processing mutations...
Structure of human pro-chymase: a model for the activating transition of granule-associated proteasesK Kinkead Reiling
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143, USA
Biochemistry 42:2616-24. 2003..The zymogen positioning of both the 180s and autolysis loops are synergistic structural elements that appear to prevent premature proteolysis by chymase and, quite possibly, by other dipeptide zymogens...
Matrix metalloproteinase-2 and -9 expression increases in Mycoplasma-infected airways but is not required for microvascular remodelingPeter Baluk
Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0130, USA
Am J Physiol Lung Cell Mol Physiol 287:L307-17. 2004..We conclude that despite major increases in expression, MMP-2 and MMP-9 are not essential for microvascular remodeling in M. pulmonis-induced chronic airway inflammation...
New developments in the genetics and activation of mast cell proteasesGeorge H Caughey
Department of Medicine, Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA 94143 0911, USA
Mol Immunol 38:1353-7. 2002....
Structure and activity of human pancreasin, a novel tryptic serine peptidase expressed primarily by the pancreasVikash J Bhagwandin
Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco, California 94143 0911, USA
J Biol Chem 278:3363-71. 2003..Thus, pancreasin is a secreted, tryptic serine protease of the pancreas with novel physical and enzymatic properties. These studies provide a rationale for exploring the natural targets and roles of this enzyme...
Lys40 but not Arg143 influences selectivity of angiotensin conversion by human alpha-chymaseDiego J Muilenburg
Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco, 90 Medical Center Way, Box 0911, San Francisco, CA 94143-0911, USA
Biochim Biophys Acta 1596:346-56. 2002..The Arg143Gln mutant, contrary to prediction, remains highly Phe8-selective. Therefore, Lys40, but not Arg143, contributes to human chymase's remarkable preference for AT II generation over destruction...
Mast cell peptidases: chameleons of innate immunity and host defenseNeil N Trivedi
Section of Pulmonary and Critical Care Medicine, Medicine Service, Veterans Affairs Medical Center, Mailstop 111 D, 4150 Clement Street, San Francisco, CA 94121, USA
Am J Respir Cell Mol Biol 42:257-67. 2010....
Mouse prostasin gene structure, promoter analysis, and restricted expression in lung and kidneyGeorge M Verghese
Department of Medicine, University of Virginia, Charlottesville, Virginia 22908 0546, USA
Am J Respir Cell Mol Biol 30:519-29. 2004..Mouse prostasin highly resembles its human ortholog in gene organization and tissue specificity, including strong expression in pulmonary epithelium, suggesting that mice will be useful for probing prostasin's functions in vivo...
Ex vivo sputum analysis reveals impairment of protease-dependent mucus degradation by plasma proteins in acute asthmaAnh L Innes
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA
Am J Respir Crit Care Med 180:203-10. 2009..Airway mucus plugs, composed of mucin glycoproteins mixed with plasma proteins, are an important cause of airway obstruction in acute severe asthma, and they are poorly treated with current therapies...
Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimensXiang Xu
Department of Medicine University of California at San Francisco, San Francisco, 94143, USA
J Heart Lung Transplant 24:1055-66. 2005....
Building a better heparinGeorge H Caughey
Cardiovascular Research Institute and Department of Medicine, University of California at San Francisco, San Francisco, California 94143, USA
Am J Respir Cell Mol Biol 28:129-32. 2003
Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actionsJames K Brown
Pulmonary and Critical Care Medicine Section, Medical Service, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA
Am J Physiol Lung Cell Mol Physiol 282:L197-206. 2002..We conclude that beta-tryptase is a potent mitogenic serine protease in cultured human airway smooth muscle cells. However, its growth stimulatory effects in these cells occur predominantly via nonproteolytic actions...
Mast cell cathepsins C and S control levels of carboxypeptidase A and the chymase, mouse mast cell protease 5Frida Henningsson
Swedish University of Agricultural Sciences, Department of Veterinary Medical Chemistry, The Biomedical Center, Box 575, S-751 23 Uppsala, Sweden
Biol Chem 384:1527-31. 2003..The present study thus indicates novel roles for cathepsins C and S in regulating the levels of stored proteases in the mast cell secretory granules...
Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarctsPorur Somasundaram
Section of Cardiovascular Sciences, DeBakey Heart Center, Baylor College of Medicine, and The Methodist Hospital, Houston, Texas 77030, USA
J Pathol 205:102-11. 2005..Endothelial PAR-2 stimulation with the agonist peptide SLIGKV induced a similar chemokine expression profile. Mast cell tryptase may exert its angiogenic effects in part through selective stimulation of angiogenic chemokines...
Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levelsCem Akin
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
Clin Immunol 123:268-71. 2007..Total and mature tryptase levels positively correlated with disease severity, as well as prothrombin time and partial thromboplastin time, and negatively correlated with the hemoglobin concentration...
Regulation of the epithelial Na+ channel by peptidasesCarole Planes
INSERM U773, Centre de Recherche Biomedicale Bichat Beaujon CRB3, Universite Paris 7, 75018 Paris, France
Curr Top Dev Biol 78:23-46. 2007..Thus, several converging lines of evidence indicate that ENaC function is regulated by peptidases, and that such regulation is critical for embryonic development and adult function of organs such as skin, kidney, and lung...
