기도 점액의 생성; 점액소의 합성, 분비 및 희석
Formation of Airway Mucus; Synthesis, Exocytosis and Dilution of Gel-Forming Mucins
1
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
The lungs are highly defensive to environmental challenges thanks to the airway mucus layer, not only as a pool of antimicrobial and antioxidant contents but also as an important part of physical barrier and mucociliary clearance. This review comprises the mechanism of airway mucus production; synthesis, exocytosis to the airway lumen and dilution of gel-forming mucins. Airway mucus consists of mainly water and mucins, highly glycosylated and condensed proteins. The mucins are produced in the mucin-secreting cells, in which interleukin-13 is one of the synthesis stimulators. Mucins are processed and maturated in the cytoplasm, and then released into the airway in two ways, constitutive and regulated. The constitutive exocytosis might be essential in maintaining normal airway mucus gel layer. The regulated exocytosis occurs mainly in the diseased airway, agonized by ATP through P2Y2 purinergic receptors. Secreted mucins are immediately hydrated through the osmotic pressure on the airway epithelium. Water and bicarbonate contents in the lumen are important factors determining the physical properties, especially the viscosity of the airway mucus.
Abstract
The lungs are highly defensive to environmental challenges thanks to the airway mucus layer, not only as a pool of antimicrobial and antioxidant contents but also as an important part of physical barrier and mucociliary clearance. This review comprises the mechanism of airway mucus production; synthesis, exocytosis to the airway lumen and dilution of gel-forming mucins. Airway mucus consists of mainly water and mucins, highly glycosylated and condensed proteins. The mucins are produced in the mucin-secreting cells, in which interleukin-13 is one of the synthesis stimulators. Mucins are processed and maturated in the cytoplasm, and then released into the airway in two ways, constitutive and regulated. The constitutive exocytosis might be essential in maintaining normal airway mucus gel layer. The regulated exocytosis occurs mainly in the diseased airway, agonized by ATP through P2Y2 purinergic receptors. Secreted mucins are immediately hydrated through the osmotic pressure on the airway epithelium. Water and bicarbonate contents in the lumen are important factors determining the physical properties, especially the viscosity of the airway mucus.
참고문헌 (50)
- Evans CM, "Mucin is produced by clara cells in the proximal airways of antigen-challenged mice", Am J Respir Cell Mol Biol, 31, pp.382~394 (2004)
- Rogers DF, "Physiology of airway mucus secretion and pathophysiology of hypersecretion", Respir Care, 52, pp.1134~1146 (2007)
- Williams IP, "Analyses of human tracheobronchial mucus from healthy subjects", Eur J Respir Dis, 63, pp.510~515 (1982)
- Williams OW, "Airway mucus: from production to secretion", Am J Respir Cell Mol Biol, 34, pp.527~536 (2006)
- Ali M, "Analysis of the proteome of human airway epithelial secretions", Proteome Sci, 9, pp.4~ (2011)
- Evans CM, "Airway mucus: the good, the bad, the sticky", Pharmacol Ther, 121, pp.332~348 (2009)
- Fahy JV, "Airway mucus function and dysfunction", N Engl J Med, 363, pp.2233~2247 (2010)
- Hoorens PR, "Genome wide analysis of the bovine mucin genes and their gastrointestinal transcription profile", BMC Genomics, 12, pp.140~ (2011)
- Guang W, "Muc1 cell surface mucin attenuates epithelial inflammation in response to a common mucosal pathogen", J Biol Chem, 285, pp.20547~2057 (2010)
- Choi S, "TNF-α is a key regulator of MUC1, an anti-inflammatory molecule, during airway Pseudomonas aeruginosa infection", Am J Respir Cell Mol Biol, 44, pp.255~260 (2011)
- Hisatsune A, "Anti-MUC1 antibody inhibits EGF receptor signaling in cancer cells", Biochem Biophys Res Commun, 405, pp.377~381 (2011)
- Young HW, "Central role of Muc5ac expression in mucous metaplasia and its regulation by conserved 5' elements", Am J Respir Cell Mol Biol, 37, pp.273~290 (2007)
- Rousseau K, "Muc5b and Muc5ac are the major oligomeric mucins in equine airway mucus", Am J Physiol Lung Cell Mol Physiol, 292, pp.L1396~L1404 (2007)
- Chen EY, "A new role for bicarbonate in mucus formation", Am J Physiol Lung Cell Mol Physiol, 299, pp.L542~L549 (2010)
- Jung SR, "Pattern of Ca2+ increase determines the type of secretory mechanism activated in dog pancreatic duct epithelial cells", J Physiol, 576, pp.163~178 (2006)
- Kesimer M, "Unpacking a gel-forming mucin: a view of MUC5B organization after granular release", Am J Physiol Lung Cell Mol Physiol, 298, pp.L15~L22 (2010)
- De Lisle RC, "Pass the bicarb: the importance of HCO3- for mucin release", J Clin Invest, 119, pp.2535~2537 (2009)
- Blank U, "The mechanisms of exocytosis in mast cells", Adv Exp Med Biol, 716, pp.107~122 (2011)
- Cosen-Binker LI, "Munc18", SNARE proteins' regulation of exocytosis in guinea pig duodenal Brunner's gland acini, 2008, pp.14, 2314~2322
- Jahn R, "Membrane fusion and exocytosis", Annu Rev Biochem, 68, pp.863~911 (1999)
- Suudhof TC, "Neurotransmitter release", Handb Exp Pharmacol, (184), pp.1~21 (2008)
- Behrendorff N, "Vesicle-associated membrane protein 8 (VAMP8) is a SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) selectively required for sequential granule-to-granule fusion", J Biol Chem, 286, pp.29627~29634 (2011)
- Liu Y, "The role of synaptobrevin1", VAMP1 in Ca2+-triggered neurotransmitter release at the mouse neuromuscular junction, 2011, pp.589, 1603~1618
- Mellander L, "Electrochemical probes for detection and analysis of exocytosis and vesicles", Chemphyschem, 11, pp.2756~2763 (2010)
- Brunger AT, "Structure and function of SNARE and SNARE-interacting proteins", Q Rev Biophys, 38, pp.1~47 (2005)
- Davis CW, "Regulated airway goblet cell mucin secretion", Annu Rev Physiol, 70, pp.487~512 (2008)
- Okada SF, "Coupled nucleotide and mucin hypersecretion from goblet- cell metaplastic human airway epithelium", Am J Respir Cell Mol Biol, 45, pp.253~260 (2011)
- Zhu Y, "Munc13-2-", - baseline secretion defect reveals source of oligomeric mucins in mouse airways, 2008, pp.586, 1977~1992
- Wan H, "Foxa2 regulates alveolarization and goblet cell hyperplasia", Development, 131, pp.953~964 (2004)
- Chen G, "SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production", J Clin Invest, 119, pp.2914~2924 (2009)
- Lai H, "New pharmacotherapy for airway mucus hypersecretion in asthma and COPD: targeting intracellular signaling pathways", J Aerosol Med Pulm Drug Deliv, 23, pp.219~231 (2010)
- Jung SR, "Control of granule mobility and exocytosis by Ca2+-dependent formation of F-actin in pancreatic duct epithelial cells", Traffic, 10, pp.392~410 (2009)
- Kreda SM, "Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells", J Physiol, 584, pp.245~259 (2007)
- Kreda SM, "Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides", J Physiol, 588, pp.2255~2267 (2010)
- Higashio H, "Doc2 alpha and Munc13-4 regulate Ca(2+)-dependent secretory lysosome exocytosis in mast cells", J Immunol, 180, pp.4774~4784 (2008)
- Mandic SA, "Munc18-1 and Munc18-2 proteins modulate beta-cell Ca2+ sensitivity and kinetics of insulin exocytosis differently", J Biol Chem, 286, pp.28026~28040 (2011)
- Chen YA, "Scheller RH. SNARE-mediated membrane fusion", Nat Rev Mol Cell Biol, 2, pp.98~106 (2001)
- Jahn R, "SNAREs--engines for membrane fusion", Nat Rev Mol Cell Biol, 7, pp.631~643 (2006)
- Brunger AT, "Structure of proteins involved in synaptic vesicle fusion in neurons", Annu Rev Biophys Biomol Struct, 30, pp.157~171 (2001)
- Groffen AJ, "Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release", Science, 327, pp.1614~1618 (2010)
- Ke B, "Doc2beta is a novel Munc18c-interacting partner and positive effector of syntaxin 4-mediated exocytosis", J Biol Chem, 282, pp.21786~21797 (2007)
- Yang X, "Complexin clamps asynchronous release by blocking a secondary Ca(2+) sensor via its accessory α helix", Neuron, 68, pp.907~920 (2010)
- Li J, "Silence of Synaptotagmin VII inhibits release of dense core vesicles in PC12 cells", Sci China C Life Sci, 52, pp.1156~1163 (2009)
- Wang P, "Synaptotagmin VII is targeted to secretory organelles in PC12 cells, where it functions as a high-affinity calcium sensor", Mol Cell Biol, 25, pp.8693~8702 (2005)
- "A transcriptome atlas database for mouse embryo" (2008)[URL]
- Tuvim MJ, "Synaptotagmin 2 couples mucin granule exocytosis to Ca2+ signaling from endoplasmic reticulum", J Biol Chem, 284, pp.9781~9787 (2009)
- Abdullah LH, "Mucin secretion and PKC isoforms in SPOC1 goblet cells: differential activation by purinergic agonist and PMA", Am J Physiol Lung Cell Mol Physiol, 285, pp.L149~L160 (2003)
- Donaldson SH, "Mucus clearance and lung function in cystic fibrosis with hypertonic saline", N Engl J Med, 354, pp.241~250 (2006)
- Daviskas E, "Effect of increasing doses of mannitol on mucus clearance in patients with bronchiectasis", Eur Respir J, 31, pp.765~772 (2008)
- Ramsey BW, "VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation", N Engl J Med, 365, pp.1663~1672 (2011)