George H Caughey

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Tryptase genetics and anaphylaxis
    George 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
  2. pmc Mast cell tryptases and chymases in inflammation and host defense
    George H Caughey
    Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA
    Immunol Rev 217:141-54. 2007
  3. pmc Guinea pig chymase is leucine-specific: a novel example of functional plasticity in the chymase/granzyme family of serine peptidases
    George H Caughey
    Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
    J Biol Chem 283:13943-51. 2008
  4. doi request reprint Mast cell proteases as protective and inflammatory mediators
    George H Caughey
    Department of Medicine, University of California at San Francisco, San Francisco, Califonia, USA
    Adv Exp Med Biol 716:212-34. 2011
  5. pmc Neutrophil histamine contributes to inflammation in mycoplasma pneumonia
    Xiang 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
  6. pmc Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors
    Kavita Raman
    Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
    J Biol Chem 288:10588-98. 2013
  7. pmc Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells
    Shilpa Nimishakavi
    Cardiovascular Research Institute, San Francisco, CA, USA
    Am J Physiol Lung Cell Mol Physiol 303:L97-106. 2012
  8. pmc Cathepsin L protects mice from mycoplasmal infection and is essential for airway lymphangiogenesis
    Xiang Xu
    Department of Medicine, University of California at San Francisco, CA 94121, USA
    Am J Respir Cell Mol Biol 49:437-44. 2013
  9. ncbi request reprint Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site
    Wilfred 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
  10. pmc Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa
    Xiang Xu
    Department of Medicine, University of California at San Francisco, San Francisco, California, USA
    J Leukoc Biol 91:275-84. 2012

Collaborators

Detail Information

Publications42

  1. pmc Tryptase genetics and anaphylaxis
    George 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...
  2. pmc Mast cell tryptases and chymases in inflammation and host defense
    George 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...
  3. pmc Guinea pig chymase is leucine-specific: a novel example of functional plasticity in the chymase/granzyme family of serine peptidases
    George 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...
  4. doi request reprint Mast cell proteases as protective and inflammatory mediators
    George H Caughey
    Department of Medicine, University of California at San Francisco, San Francisco, Califonia, USA
    Adv Exp Med Biol 716:212-34. 2011
    ....
  5. pmc Neutrophil histamine contributes to inflammation in mycoplasma pneumonia
    Xiang 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...
  6. pmc Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors
    Kavita Raman
    Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
    J Biol Chem 288:10588-98. 2013
    ..Similar pathways appear to have been traversed by prosemins and tryptases, suggesting that mutational tail loss is an important means of evolving new functions of tryptic serine proteases from transmembrane ancestors...
  7. pmc Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells
    Shilpa 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...
  8. pmc Cathepsin L protects mice from mycoplasmal infection and is essential for airway lymphangiogenesis
    Xiang Xu
    Department of Medicine, University of California at San Francisco, CA 94121, USA
    Am J Respir Cell Mol Biol 49:437-44. 2013
    ....
  9. ncbi request reprint Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site
    Wilfred 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...
  10. pmc Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa
    Xiang 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...
  11. doi request reprint How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolution
    Wilfred W Raymond
    Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA 94143, USA
    J Immunol 185:5360-8. 2010
    ....
  12. pmc Mast cell alpha and beta tryptases changed rapidly during primate speciation and evolved from gamma-like transmembrane peptidases in ancestral vertebrates
    Neil N Trivedi
    Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, CA 94143, USA
    J Immunol 179:6072-9. 2007
    ....
  13. pmc Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma
    Ryan 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...
  14. pmc Mast cells protect mice from Mycoplasma pneumonia
    Xiang 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
    ..Mice infected with Mycoplasma pulmonis can develop localized, life-long airway infection accompanied by persistent inflammation and remodeling...
  15. pmc Mast cell and neutrophil peptidases attack an inactivation segment in hepatocyte growth factor to generate NK4-like antagonists
    Wilfred 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
    ..Thus, HGF possesses an "inactivation segment" that serves as an Achilles' heel attacked by inflammatory proteases. This work reveals a potential physiological pathway for inactivation of HGF and generation of NK4-like antagonists...
  16. ncbi request reprint Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line
    Zhenyue 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
    ....
  17. pmc Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice
    Rachel E Sutherland
    Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 6:e27564. 2011
    ....
  18. pmc Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor
    George 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...
  19. pmc Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and creates a reservoir of angiotensin II-generating activity
    Wilfred W Raymond
    Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA 94143, USA
    J Immunol 182:5770-7. 2009
    ....
  20. pmc Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss-of-function mutations
    Neil 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...
  21. ncbi request reprint Mastin is a gelatinolytic mast cell peptidase resembling a mini-proteasome
    Wilfred 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
    ....
  22. pmc Cathepsins L and S are not required for activation of dipeptidyl peptidase I (cathepsin C) in mice
    Jon 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...
  23. pmc Protease-activated receptor 2, dipeptidyl peptidase I, and proteases mediate Clostridium difficile toxin A enteritis
    Graeme 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...
  24. pmc Mast cell dipeptidyl peptidase I mediates survival from sepsis
    Jon 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...
  25. pmc The αvβ6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells
    Kotaro Sugimoto
    Lung Biology Center, Department of Medicine, UCSF, San Francisco, California, USA
    J Clin Invest 122:748-58. 2012
    ....
  26. doi request reprint Chimerism, point mutation, and truncation dramatically transformed mast cell delta-tryptases during primate evolution
    Neil 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...
  27. ncbi request reprint Matrix metalloproteinase-2 and -9 expression increases in Mycoplasma-infected airways but is not required for microvascular remodeling
    Peter 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...
  28. ncbi request reprint New developments in the genetics and activation of mast cell proteases
    George 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
    ....
  29. ncbi request reprint Structure of human pro-chymase: a model for the activating transition of granule-associated proteases
    K 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...
  30. pmc Association of large-airway lymphocytic bronchitis with bronchiolitis obliterans syndrome
    John R Greenland
    Department of Medicine, University of California at San Francisco, San Francisco, CA 94121, USA
    Am J Respir Crit Care Med 187:417-23. 2013
    ..Although acute rejection and lymphocytic bronchiolitis have been identified as risk factors for the development of BOS, it is unclear whether large-airway lymphocytic inflammation conveys the same risk...
  31. ncbi request reprint Lys40 but not Arg143 influences selectivity of angiotensin conversion by human alpha-chymase
    Diego 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...
  32. pmc Mast cell peptidases: chameleons of innate immunity and host defense
    Neil 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
    ....
  33. ncbi request reprint Structure and activity of human pancreasin, a novel tryptic serine peptidase expressed primarily by the pancreas
    Vikash 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...
  34. ncbi request reprint Mouse prostasin gene structure, promoter analysis, and restricted expression in lung and kidney
    George 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...
  35. pmc Ex vivo sputum analysis reveals impairment of protease-dependent mucus degradation by plasma proteins in acute asthma
    Anh 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...
  36. pmc Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimens
    Xiang Xu
    Department of Medicine University of California at San Francisco, San Francisco, 94143, USA
    J Heart Lung Transplant 24:1055-66. 2005
    ..Early detection is hindered by inadequate tests and an incomplete understanding of the molecular events preceding or accompanying graft deterioration...
  37. ncbi request reprint Building a better heparin
    George 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
  38. ncbi request reprint Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions
    James 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...
  39. ncbi request reprint Mast cell cathepsins C and S control levels of carboxypeptidase A and the chymase, mouse mast cell protease 5
    Frida 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...
  40. pmc Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts
    Porur 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...
  41. pmc Regulation of the epithelial Na+ channel by peptidases
    Carole 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...
  42. pmc Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels
    Cem 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...