Evaluation of the substrate specificity of human mast cell tryptase beta I and demonstration of its importance in bacterial infections of the lung - PubMed (original) (raw)
. 2001 Jul 13;276(28):26276-84.
doi: 10.1074/jbc.M102356200. Epub 2001 May 2.
Affiliations
- PMID: 11335723
- DOI: 10.1074/jbc.M102356200
Free article
Evaluation of the substrate specificity of human mast cell tryptase beta I and demonstration of its importance in bacterial infections of the lung
C Huang et al. J Biol Chem. 2001.
Free article
Abstract
Human pulmonary mast cells (MCs) express tryptases alpha and beta I, and both granule serine proteases are exocytosed during inflammatory events. Recombinant forms of these tryptases were generated for the first time to evaluate their substrate specificities at the biochemical level and then to address their physiologic roles in pulmonary inflammation. Analysis of a tryptase-specific, phage display peptide library revealed that tryptase beta I prefers to cleave peptides with 1 or more Pro residues flanked by 2 positively charged residues. Although recombinant tryptase beta I was unable to activate cultured cells that express different types of protease-activated receptors, the numbers of neutrophils increased >100-fold when enzymatically active tryptase beta I was instilled into the lungs of mice. In contrast, the numbers of lymphocytes and eosinophils in the airspaces did not change significantly. More important, the tryptase beta I-treated mice exhibited normal airway responsiveness. Neutrophils did not extravasate into the lungs of tryptase alpha-treated mice. Thus, this is the first study to demonstrate that the two nearly identical human MC tryptases are functionally distinct in vivo. When MC-deficient W/W(v) mice were given enzymatically active tryptase beta I or its inactive zymogen before pulmonary infection with Klebsiella pneumoniae, tryptase beta I-treated W/W(v) mice had fewer viable bacteria in their lungs relative to zymogen-treated W/W(v) mice. Because neutrophils are required to combat bacterial infections, human tryptase beta I plays a critical role in the antibacterial host defenses of the lung by recruiting neutrophils in a manner that does not alter airway reactivity.
Similar articles
- cDNA sequence of two sheep mast cell tryptases and the differential expression of tryptase and sheep mast cell proteinase-1 in lung, dermis and gastrointestinal tract.
Pemberton AD, McAleese SM, Huntley JF, Collie DD, Scudamore CL, McEuen AR, Walls AF, Miller HR. Pemberton AD, et al. Clin Exp Allergy. 2000 Jun;30(6):818-32. doi: 10.1046/j.1365-2222.2000.00831.x. Clin Exp Allergy. 2000. PMID: 10848900 - Biochemical and functional characterization of human transmembrane tryptase (TMT)/tryptase gamma. TMT is an exocytosed mast cell protease that induces airway hyperresponsiveness in vivo via an interleukin-13/interleukin-4 receptor alpha/signal transducer and activator of transcription (STAT) 6-dependent pathway.
Wong GW, Foster PS, Yasuda S, Qi JC, Mahalingam S, Mellor EA, Katsoulotos G, Li L, Boyce JA, Krilis SA, Stevens RL. Wong GW, et al. J Biol Chem. 2002 Nov 1;277(44):41906-15. doi: 10.1074/jbc.M205868200. Epub 2002 Aug 22. J Biol Chem. 2002. PMID: 12194977 - Human tryptases alpha and beta/II are functionally distinct due, in part, to a single amino acid difference in one of the surface loops that forms the substrate-binding cleft.
Huang C, Li L, Krilis SA, Chanasyk K, Tang Y, Li Z, Hunt JE, Stevens RL. Huang C, et al. J Biol Chem. 1999 Jul 9;274(28):19670-6. doi: 10.1074/jbc.274.28.19670. J Biol Chem. 1999. PMID: 10391906 - Protease-proteoglycan complexes of mouse and human mast cells and importance of their beta-tryptase-heparin complexes in inflammation and innate immunity.
Stevens RL, Adachi R. Stevens RL, et al. Immunol Rev. 2007 Jun;217:155-67. doi: 10.1111/j.1600-065X.2007.00525.x. Immunol Rev. 2007. PMID: 17498058 Review. - Biology of mast cell tryptase. An inflammatory mediator.
Hallgren J, Pejler G. Hallgren J, et al. FEBS J. 2006 May;273(9):1871-95. doi: 10.1111/j.1742-4658.2006.05211.x. FEBS J. 2006. PMID: 16640553 Review.
Cited by
- Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification.
Tu J, Li W, Hansbro PM, Yan Q, Bai X, Donovan C, Kim RY, Galvao I, Das A, Yang C, Zou J, Diwan A. Tu J, et al. Mol Ther. 2023 Aug 2;31(8):2524-2542. doi: 10.1016/j.ymthe.2023.06.010. Epub 2023 Jun 19. Mol Ther. 2023. PMID: 37340635 Free PMC article. - Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia.
Le QT, Lyons JJ, Naranjo AN, Olivera A, Lazarus RA, Metcalfe DD, Milner JD, Schwartz LB. Le QT, et al. J Exp Med. 2019 Oct 7;216(10):2348-2361. doi: 10.1084/jem.20190701. Epub 2019 Jul 23. J Exp Med. 2019. PMID: 31337736 Free PMC article. - Tryptase as a polyfunctional component of mast cells.
Atiakshin D, Buchwalow I, Samoilova V, Tiemann M. Atiakshin D, et al. Histochem Cell Biol. 2018 May;149(5):461-477. doi: 10.1007/s00418-018-1659-8. Epub 2018 Mar 12. Histochem Cell Biol. 2018. PMID: 29532158 Review. - Neutrophilia, gelatinase release and microvascular leakage induced by human mast cell tryptase in a mouse model: Lack of a role of protease-activated receptor 2 (PAR2).
Khedr MEMS, Abdelmotelb AM, Pender SLF, Zhou X, Walls AF. Khedr MEMS, et al. Clin Exp Allergy. 2018 May;48(5):555-567. doi: 10.1111/cea.13108. Clin Exp Allergy. 2018. PMID: 29383785 Free PMC article. - Divergent Inhibitor Susceptibility among Airway Lumen-Accessible Tryptic Proteases.
Nimishakavi S, Raymond WW, Gruenert DC, Caughey GH. Nimishakavi S, et al. PLoS One. 2015 Oct 20;10(10):e0141169. doi: 10.1371/journal.pone.0141169. eCollection 2015. PLoS One. 2015. PMID: 26485396 Free PMC article.