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Mechanisms of Acid and Base Secretion by the Airway Epithelium

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Abstract

One of the main functions of the airway epithelium is to inactivate and remove infectious particles from inhaled air and thereby prevent infection of the distal lung. This function is achieved by mucociliary and cough clearance and by antimicrobial factors present in the airway surface liquid (ASL). There are indications that airway defenses are affected by the pH of the ASL and historically, acidification of the airway surfaces has been suggested as a measure of airway disease. However, even in health, the ASL is slightly acidic, and this acidity might be part of normal airway defense. Only recently research has focused on the mechanisms responsible for acid and base secretion into the ASL. Advances resulted from research into the airway disease associated with cystic fibrosis (CF) after it was found that the CFTR Cl channel conducts HCO 3 and, therefore, may contribute to ASL pH. However, the acidity of the ASL indicated parallel mechanisms for H+ secretion. Recent investigations identified several H+ transporters in the apical membrane of the airway epithelium. These include H+ channels and ATP-driven H+ pumps, including a non-gastric isoform of the H+-K+ ATPase and a vacuolar-type H+ ATPase. Current knowledge of acid and base transporters and their potential roles in airway mucosal pH regulation is reviewed here.

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References

  1. Acevedo M., Steele L.W. 1993. Na+-H+ exchanger in isolated epithelial tracheal cells from sheep. Involvement in tracheal proton secretion. Exp. Physiol. 78:383–394

    PubMed  CAS  Google Scholar 

  2. Adler K., Wooten O., Philippoff W., Lerner E., Dulfano M. 1972. Physical properties of sputum. 3. Rheologic variability and intrinsic relationships. Am. Rev. Respir. Dis. 106:86–96

    PubMed  CAS  Google Scholar 

  3. Alton E.W.F.W., Currie A.D., Logan-Sinclair R., Warner J.O., Hodson M.E., Geddes D.M. 1990. Nasal potential difference: a clinical test for cystic fibrosis. Eur. Resp. J. 3:922–926

    CAS  Google Scholar 

  4. Awayda M.S., Boudreaux M.J., Reger R.L., Hamm L.L. 2000. Regulation of the epithelial Na+ channel by extracellular acidification. Am. J. Physiol. 279:C1896–1905

    CAS  Google Scholar 

  5. Bachmann O., Riederer B., Rossmann H., Groos S., Schultheis P.J., Shull G.E., Gregor M., Manns M.P., Seidler U. 2004. The Na+/H+ exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation. Am. J. Physiol. 287:G125–G133

    CAS  Google Scholar 

  6. Ballard S.T., Trout L., Garrison J., Inglis S.K. 2005. Ionic mechanism of forskolin-induced liquid secretion by porcine bronchi. Am. J. Physiol. 290:L97–L104

    Google Scholar 

  7. Boat T.F., Cheng P.W. 1980. Biochemistry of airway mucus secretions. Fed. Proc. 39:3067–74

    PubMed  CAS  Google Scholar 

  8. Bodem C., Lampton L., Miller D., Tarka E., Everett E. 1983. Endobronchial pH. Relevance of aminoglycoside activity in gram-negative bacillary pneumonia. Am. Rev. Respir. Dis. 127:39–41

    PubMed  CAS  Google Scholar 

  9. Boers J.E., Ambergen A.W., Thunnissen F.B.J.M. 1999. Number and Proliferation of Clara Cells in Normal Human Airway Epithelium. Am. J. Respir. Crit. Care Med. 159:1585–1591

    PubMed  CAS  Google Scholar 

  10. Boucher R.C. 1999. Molecular insights into the physiologyof the ‘thin film’ of airway surface liquid. J. Physiol. Lond. 516:631–638

    PubMed  CAS  Google Scholar 

  11. Bowman E.J., Siebers A., Altendorf K. 1988. Bafilomycins: A Class of Inhibitors of Membrane ATPases from Microorganisms, Animal Cells, and Plant Cells. Proc. Natl. Acad. Sci. USA 85:7972–7976

    PubMed  CAS  Google Scholar 

  12. Breuninger H. 1964. Über das physikalisch-chemische Verhalten des Nasenschleims. Eur. Arch. Oto-Rhino-Laryng. 184:133–138

    CAS  Google Scholar 

  13. Byeon M., Westerman M., Maroulakou I., Henderson K., Suster S., Zhang X., Papas T., Vesely J., Willingham M., Green J., Schweinfest C. 1996. The downregulated in adenoma (DRA) gene encodes an intestine-specific membrane glycoprotein. Oncogene 12:387–396

    PubMed  CAS  Google Scholar 

  14. Chalfant M.L., Denton J.S., Berdiev B.K., Ismailov I.I., Benos D.J., Stanton B.A. 1999. Intracellular H+ regulates the alpha-subunit of ENaC, the epithelial Na+ channel. Am. J. Physiol. Cell Physiol. 276:C477–C486

    PubMed  CAS  Google Scholar 

  15. Ciaccio C., De Sanctis G., Marini S., Sinibaldi F., Santucci R., Arcovito A., Bellelli A., Ghibaudi E., Ferrari Rosa P., Coletta M. 2004. Proton Linkage for CO Binding and Redox Properties of Bovine Lactoperoxidase. Biophys. J. 86:448–454

    Article  PubMed  CAS  Google Scholar 

  16. Clarke L.L., Paradiso A.M., Boucher R.C. 1992. Histamine-induced Cl secretion in human nasal epithelium: responses of apical and basolateral membranes. Am. J. Physiol. 263:C1190–C119

    PubMed  CAS  Google Scholar 

  17. Coakley R.D., Grubb B.R., Paradiso A.M., Gatzy J.T., Johnson L.G., Kreda S.M., O’Neal W.K., Boucher R.C. 2003. Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium. Proc. Natl. Acad. Sci. USA 100:16083–16088

    PubMed  CAS  Google Scholar 

  18. Conner G.E., Salathe M., Forteza R. 2002. Lactoperoxidase and Hydrogen Peroxide Metabolism in the Airway. Am. J. Respir. Crit. Care Med. 166:57S–61S

    Google Scholar 

  19. Cotton C.U., Stutts M.J., Knowles M.R., Gatzy J.T., Boucher R.C. 1987. Abnormal apical cell membrane in cystic fibrosis respiratory epithelium. An in vitro electrophysiologic analysis. J. Clin. Invest. 79:80–85

    PubMed  CAS  Google Scholar 

  20. DeCoursey T., Cherny V. 1995. Voltage-activated proton currents in membrane patches of rat alveolar epithelial cells. J. Physiol. 489:299–307

    PubMed  CAS  Google Scholar 

  21. DeCoursey T.E. 2003. Voltage-gated proton channels and other proton transfer pathways. Physiol. Rev. 83:475–579

    PubMed  CAS  Google Scholar 

  22. DeCoursey, T.E. 2004. During the Respiratory Burst, Do Phagocytes Need Proton Channels or Potassium Channels or Both? Sci. STKE 2004:pe21

  23. Del Castillo J.R., Rajendran V.M., Binder H.J. 1991. Apical membrane localization of ouabain-sensitive K+-activated ATPase activities in rat distal colon. Am. J. Physiol. 261:G1005–G1011

    PubMed  Google Scholar 

  24. Devor D.C., Bridges R.J., Pilewski J.M. 2000. Pharmacological modulation of ion transport across wild-type and ΔF508 CFTR-expressing human bronchial epithelia. Am. J. Physiol. 279:C461–C479

    CAS  Google Scholar 

  25. Devor D.C., Singh A.K., Lambert L.C., DeLuca A., Frizzell R.A., Bridges R.J. 1999. Bicarbonate and chloride secretion in Calu-3 human airway epithelial cells. J. Gen. Physiol. 113:743–760

    PubMed  CAS  Google Scholar 

  26. DiPaola M., Maxfield F. 1984. Conformational changes in the receptors for epidermal growth factor and asialoglycoproteins induced by the mildly acidic pH found in endocytic vesicles. J. Biol. Chem. 259:9163–9171

    PubMed  CAS  Google Scholar 

  27. Dubin R.F., Robinson S.K., Widdicombe J.H. 2004. Secretion of lactoferrin and lysozyme by cultures of human airway epithelium. Am. J. Physiol. 286:L750–L755

    CAS  Google Scholar 

  28. Dudeja P.K., Hafez N., Tyagi S., Gailey C.A., Toofanfard M., Alrefai W.A., Nazir T.M., Ramaswamy K., Al-Bazzaz F.J. 1999. Expression of the Na+/H+ and Cl/HCO 3 exchanger isoforms in proximal and distal human airways. Am. J. Physiol. 276:L971–L978

    PubMed  CAS  Google Scholar 

  29. England R., Homer J., Knight L., Ell S. 1999. Nasal pH measurement: a reliable and repeatable parameter. Clin. Otolaryngol. Allied Sci. 24:67–68

    PubMed  CAS  Google Scholar 

  30. Fabricant N.D. 1941. Significance of the pH of nasal secretions in situ. Arch. Otolaryngology 34:150–163

    CAS  Google Scholar 

  31. Fischer H., Widdicombe J.H., Illek B. 2002. Acid secretion and proton conductance in human airway epithelium. Am. J. Physiol. Cell Physiol. 282:C736–C743

    PubMed  CAS  Google Scholar 

  32. Forgac M. 1999. Structure and properties of the vacuolar H+-ATPases. J. Biol. Chem. 274:12951–12954

    PubMed  CAS  Google Scholar 

  33. Forteza R., Salathe M., Miot F., Forteza R., Conner G.E. 2005. Regulated Hydrogen Peroxide Production by Duox in Human Airway Epithelial Cells. Am. J. Respir. Cell Mol. Biol. 32:462–469

    PubMed  CAS  Google Scholar 

  34. Ganz T. 2002. Antimicrobial polypeptides in host defense of the respiratory tract. J. Clin. Invest. 109:693–697

    PubMed  CAS  Google Scholar 

  35. Gatto L. 1981. pH of mucus in rat trachea. J. Appl. Physiol. 50:1224–1226

    PubMed  CAS  Google Scholar 

  36. Gatto L. 1985. pH of mucus in rabbit trachea: cholinergic stimulation and block. Lung 163:109–115

    PubMed  CAS  Google Scholar 

  37. Geiszt M., Witta J., Baffi J., Lekstrom K., Leto T.L. 2003. Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J. 17:1502–1504

    PubMed  CAS  Google Scholar 

  38. Granger D., Marsolais M., Burry J., Laprade R. 2002. V-type H+-ATPase in the human eccrine sweat duct: immunolocalization and functional demonstration. Am. J. Physiol. 282:C1454–C1460

    CAS  Google Scholar 

  39. Gray M.A., Pollard C.E., Harris A., Coleman L., Greenwell J.R., Argent B.E. 1990. Anion selectivity and block of the small-conductance chloride channel on pancreatic duct cells Am. J. Physiol 259:C752–C761

    PubMed  CAS  Google Scholar 

  40. Greeley T., Shumaker H., Wang Z., Schweinfest C.W., Soleimani M. 2001. Downregulated in adenoma and putative anion transporter are regulated by CFTR in cultured pancreatic duct cells. Am. J. Physiol. 281:G1301–G1308

    CAS  Google Scholar 

  41. Guerrin F., Voisin C., Macquet V., Robin H., Lequien P. 1971. Apport de la pH metrie bronchique in situ. Progr. Respir. Res 6:372–383

    Google Scholar 

  42. Guerrin F., Voisin C., Macquet V., Robin H., Wattel F., Boulanger J. 1969. Possibilities de la pH metrie bronchique in situ. In: Hypersecretion Bronchique. pp. 249–256. Clinchy, Poinsot

  43. Harkema J.R., Mariassy A., St. George J.A., Hyde D., Plopper C.G. 1991. Epithelial cells of the conducting airways. A species comparison. In: The Airway Epithelium: Physiology, Pathology, and Pharmacology. S.G. Farmer, D.W.P. Hay, editors. Marcel Dekker, Inc, New York. pp. 3–39

    Google Scholar 

  44. Harper R.W., Xu C., Eiserich J., Chen Y., Kao C.-Y., Thai P., Setiadi H., Wu R. 2005. Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium. FEBSh Lett. 579:4911–4917

    PubMed  CAS  Google Scholar 

  45. Hehar S., Mason J., Stephen A., Washington N., Jones N., Jackson S., Bush D. 1999. Twenty-four hour ambulatory nasal pH monitoring. Clin. Otolaryngol. Allied Sci. 24:24–25

    PubMed  CAS  Google Scholar 

  46. Hilding A. 1930. The common cold. Arch. Otolaryng. 12:133

    Google Scholar 

  47. Hoglund P., Haila S., Socha J., Tomaszewski L., Saarialho-Kere U., Karjalainen-Lindsberg M., Airola K., Holmberg C., de la Chapelle A., Kere J. 1996. Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. Nat. Genet. 14:316–139

    PubMed  CAS  Google Scholar 

  48. Holma B. 1985. Influence of buffer capacity and pH-dependent rheological properties of respiratory mucus on health effects due to acidic pollution. Sci. Total Environ. 41:101–123

    PubMed  CAS  Google Scholar 

  49. Holma B., Hegg P.O. 1989. pH and protein-dependent buffer capacity and viscosity of respiratory mucus: their interrelationships and influence on health. Sci. Total Environ. 84:71–82

    PubMed  CAS  Google Scholar 

  50. Illek B., W.-K.Tam A., Fischer H., Machen T.E. 1999. Anion selectivity of apical membrane conductance of Calu 3 human airway epithelia. Pfluegers Arch. 437:812–822

    CAS  Google Scholar 

  51. Illek B., Yankaskas J.R., Machen T.E. 1997. cAMP and genistein stimulate HCO 3 conductance through CFTR in human airway epithelia. Am. J. Physiol. Lung Cell. Mol. Physiol. 272:L752–L761

    CAS  Google Scholar 

  52. Inglis S.K., Finlay L., Ramminger S.J., Richard K., Ward M.R., Wilson S.M., Olver R.E. 2002. Regulation of intracellular pH in Calu-3 human airway cells. J. Physiol. 538:527–539

    PubMed  CAS  Google Scholar 

  53. Inglis S.K., Wilson S.M., Olver R.E. 2003. Secretion of acid and base equivalents by intact distal airways. Am. J. Physiol. 284:L855–L862

    CAS  Google Scholar 

  54. Ireson N.J., Tait J.S., MacGregor G.A., Baker E.H. 2001. Comparison of nasal pH values in black and white individuals with normal and high blood pressure. Clin. Sci. 100:327–333

    PubMed  CAS  Google Scholar 

  55. Jankowski A., Grinstein S. 2002. Modulation of the cytosolic and phagosomal pH by the NADPH oxidase. Antioxid. Redox Signal. 4:61–68

    PubMed  CAS  Google Scholar 

  56. Jayaraman S., Song Y., Verkman A.S. 2001. Airway surface liquid osmolality measured using fluorophore-encapsulated liposomes. J. Gen. Physiol. 117:423–430

    PubMed  CAS  Google Scholar 

  57. Jayaraman S., Song Y., Verkman A.S. 2001. Airway surface liquid pH in welldifferentiated airway epithelial cell cultures and mouse trachea. Am. J. Physiol. 281:C1504–C1511

    CAS  Google Scholar 

  58. Jayaraman S., Song Y., Vetrivel L., Shankar L., Verkman A.S. 2001. Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH. J. Clin. Invest. 107:317–324

    PubMed  CAS  Google Scholar 

  59. Knowles M.R., Buntin W.H., Bromberg P.A., Gatzy J.T., Boucher R.C. 1982. Measurements of transepithelial electric potential differences in the trachea and bronchi of human subjects in vivo. Am. Rev. Respir. Dis. 126:108–112

    PubMed  CAS  Google Scholar 

  60. Kondo M., Finkbeiner W.E., Widdicombe J.H. 1992. Cultures of bovine tracheal epithelium with differentiated ultrastructure and ion transport. In Vitro Cell. Dev. Biol. 29A:19–24

    Google Scholar 

  61. Kreda S.M., Mall M., Mengos A., Rochelle L., Yankaskas J., Riordan J.R., Boucher R.C. 2005. Characterization of wild-type and DF508 cystic fibrosis transmembrane regulator in human respiratory epithelia. Mol. Biol. Cell 16:2154–2167

    PubMed  CAS  Google Scholar 

  62. Krouse M.E., Talbott J.F., Lee M.M., Joo N.S., Wine J.J. 2004. Acid and base secretion in the Calu-3 model of human serous cells. Am. J. Physiol. 287:L1274–L1283

    CAS  Google Scholar 

  63. Kyle H., Ward J.P., Widdicombe J.G. 1990. Control of pH of airway surface liquid of the ferret trachea in vitro. J. Appl. Physiol. 68:135–140

    PubMed  CAS  Google Scholar 

  64. Lee M.C., Penland C.M., Widdicombe J.H., Wine J.J. 1998. Evidence that Calu-3 human airway cells secrete bicarbonate. Am. J. Physiol. 274:L450–L453

    PubMed  CAS  Google Scholar 

  65. Linsdell P., Tabcharani J.A., Rommens J.M., Hou Y.X., Chang X.B., Tsui L.C., Riordan J.R., Hanrahan J.W. 1997. Permeability of wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels to polyatomic anions. J. Gen. Physiol. 110:355–364

    PubMed  CAS  Google Scholar 

  66. Loffing J., Moyer B.D., Reynolds D., Shmukler B.E., Alper S.L., Stanton B.A. 2000. Functional and molecular characterization of an anion exchanger in airway serous epithelial cells. Am. J. Physiol. 279:C1016–C1023

    CAS  Google Scholar 

  67. Lucas A., Douglas L. 1934. Principles underlying ciliary activity in the respiratory tract. II. A comparison of nasal clearance in man, monkey and other mammals. Arch. Otolaryngol. 20:518–541

    Google Scholar 

  68. McShane D., Davies J.C., Davies M.G., Bush A., Geddes D.M., Alton E.W.F.W. 2003. Airway surface pH in subjects with cystic fibrosis. Eur. Respir. J. 21:37–42

    PubMed  CAS  Google Scholar 

  69. Melvin J.E., Park K., Richardson L., Schultheis P.J., Shull G.E. 1999. Mouse downregulated in adenoma (DRA) Is an Intestinal Cl/HCO 3 exchanger and is up-regulated in colon of mice lacking the NHE3 Na+/H+ exchanger. J. Biol. Chem. 274:22855–22861

    PubMed  CAS  Google Scholar 

  70. Metheny N., Stewart B., Smith L., Yan H., Diebold M., Clouse R. 1999. pH and concentration of bilirubin in feeding tube aspirates as predictors of tube placement. Nurs. Res. 48:189–197

    PubMed  CAS  Google Scholar 

  71. Mittermaier R. 1930. Untersuchungen über die Wasserstoffionenkonzentration an Sekreten und Schleimhäuten, im besonderen bei chronischen Nebenhöhlenerkrankungen. Eur. Arch. Oto-Rhino-Laryngol. 127:149–172

    Google Scholar 

  72. Murphy R., Cherny V.V., Morgan D., DeCoursey T.E. 2005. Voltage-gated proton channels help regulate pHi in rat alveolar epithelium. Am. J. Physiol. 288:L398–L408

    CAS  Google Scholar 

  73. Palmer L., Merrill W., Niederman M., Ferranti R., Reynolds H. 1986. Bacterial adherence to respiratory tract cells. Relationships between in vivo and in vitro pH and bacterial attachment. Am. Rev. Respir. Dis. 133:784–788

    PubMed  CAS  Google Scholar 

  74. Paradiso A.M. 1992. Identification of Na+-H+ exchange in human normal and cystic fibrotic ciliated airway epithelium. Am. J. Physiol. 262:L757–L764

    PubMed  CAS  Google Scholar 

  75. Paradiso A.M. 1997. ATP-activated basolateral Na+/H+ exchange in human normal and cystic fibrosis airway epithelium. Am. J. Physiol. 273:L148–L158

    PubMed  CAS  Google Scholar 

  76. Paradiso A.M., Boucher R.C. 2003. Normal and cystic fibrosis human bronchial epithelial cells exhibit negligible proton conductance across their apical membranes (Abstract). Ped. Pulmonol. Suppl. 25:233

    Google Scholar 

  77. Paradiso A.M., Coakley R.D., Boucher R.C. 2003. Polarized distribution of HCO3− transport in human normal and cystic fibrosis nasal epithelia. J. Physiol. 548:203–218

    PubMed  CAS  Google Scholar 

  78. Plopper C.G., Hyde D.M., Buckpitt A.R. 1997. Clara cells. In: The Lung: Scientific Foundations. R.G. Crystal, J.B. West, E.R. Weibel, P.J. Barnes, editors Lippincott-Raven, Philadelphia pp. 517–534

    Google Scholar 

  79. Poulsen J.H., Fischer H., Illek B., Machen T.E. 1994. Bicarbonate conductance and pH regulatory capability of cystic fibrosis transmembrane conductance regulator. Proc. Natl. Acad. Sci. USA 91:5340–4

    PubMed  CAS  Google Scholar 

  80. Poulsen J.H., Machen T.E. 1996. HCO3−dependent pHi regulation in tracheal epithelial cells. Pfluegers Arch. 432:546–554

    CAS  Google Scholar 

  81. Quinton P.M. 2001. The neglected ion: HCO 3 . Nat. Med. 7:292–293

    PubMed  CAS  Google Scholar 

  82. Reddy M.M., Kopito R.R., Quinton P.M. 1998. Cytosolic pH regulates GCl through control of phosphorylation states of CFTR. Am. J. Physiol. 275:C1040–C1047

    PubMed  CAS  Google Scholar 

  83. Ricciardolo F.L.M., Gaston B., Hunt J. 2004. Acid stress in the pathology of asthma. J. Allergy Clin. Immunol. 113:610–619

    PubMed  CAS  Google Scholar 

  84. Rogers A.V., Dewar A., Corrin B., Jeffery P.K. 1993. Identification of serous-like cells in the surface epithelium of human bronchioles. Eur. Respir. J. 6:498–504

    PubMed  CAS  Google Scholar 

  85. Rose M.C. 1992. Mucins: structure, function, and role in pulmonary diseases. Am. J. Physiol. 263:L413–L429

    PubMed  CAS  Google Scholar 

  86. Schwarzer C., Machen T.E., Illek B., Fischer H. 2004. NADPH oxidase-dependent acid production in airway epithelial cells. J. Biol. Chem. 279:36454–36461

    PubMed  CAS  Google Scholar 

  87. Shen B.Q., Finkbeiner W.E., Wine J.J., Mrsny R.J., Widdicombe J.H. 1994. Calu-3: a human airway epithelial cell line that shows cAMP-dependent Cl secretion. Am. J. Physiol. 266:L493–L501

    PubMed  CAS  Google Scholar 

  88. Sleigh M.A., Blake J.R., Liron N. 1988. The propulsion of mucus by cilia. Am Rev Respir Dis 137:726–741

    PubMed  CAS  Google Scholar 

  89. Smith J.J., Welsh M.J. 1992. cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia. J. Clin. Invest. 89:1148–1153

    Article  PubMed  CAS  Google Scholar 

  90. Sohma Y., Gray M., Imai Y., Argent B. 2001. 150 mM HCO 3 - how does the pancreas do it? Clues from computer modelling of the duct cell. J. Pancreas (Online) 2:198–202

    CAS  Google Scholar 

  91. Song Y., Salinas D., Nielson D.W., Verkman A.S. 2006. Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis. Am. J. Physiol. 290:C741–C749

    CAS  Google Scholar 

  92. Song Y., Thiagarajah J., Verkman A.S. 2003. Sodium and Chloride Concentrations, pH, and Depth of Airway Surface Liquid in Distal Airways. J. Gen. Physiol. 122:511–519

    PubMed  CAS  Google Scholar 

  93. Steinmann E. 1956. La secretion bronchique et le pH. Bronches 6:126–129

    Google Scholar 

  94. Tamada T., Hug M.J., Frizzell R.A., Bridges R.J. 2001. Microelectrode and impedance analysis of anion secretion in Calu-3 cells. J. Pancreas (Online) 2:219–228

    CAS  Google Scholar 

  95. Tandler B. 1962. Ultrastructure of the human submaxillary gland. I. Architecture and histological relationships of the secretory cells. Am. J. Anat. 111:287–307

    PubMed  CAS  Google Scholar 

  96. Tarran R., Grubb B.R., Gatzy J.T., Davis C.W., Boucher R.C. 2001. The Relative Roles of Passive Surface Forces and Active Ion Transport in the Modulation of Airway Surface Liquid Volume and Composition. J. Gen. Physiol. 118:223–236

    PubMed  CAS  Google Scholar 

  97. Thomas R.C., Meech R.W. 1982. Hydrogen ion currents and intracellular pH in depolarized voltage-clamped snail neurones. Nature 299:826–828

    PubMed  CAS  Google Scholar 

  98. Wang Z., Petrovic S., Mann E., Soleimani M. 2002. Identification of an apical Cl/HCO 3 exchanger in the small intestine. Am. J. Physiol. 282:G573–G579

    CAS  Google Scholar 

  99. Wanner A., Salathe M., O’Riordan T.G. 1996. Mucociliary clearance in the airways. Am. J. Respir. Crit. Care Med. 154:1868–1902

    PubMed  CAS  Google Scholar 

  100. Weibel E.R. 1963. Morphometry of the Human Lung. Heidelberg: Springer-Verlag

    Google Scholar 

  101. Wheat V.J., Shumaker H., Burnham C., Shull G.E., Yankaskas J.R., Soleimani M. 2000. CFTR induces the expression of DRA along with Cl/HCO 3 exchange activity in tracheal epithelial cells. Am. J. Physiol. 279:C62–C71

    CAS  Google Scholar 

  102. Widdicombe J.G. 1995. Relationships among the composition of mucus, epithelial lining liquid, and adhesion of microorganisms. Am. J. Respir. Crit. Care Med. 151:2088–2092

    PubMed  CAS  Google Scholar 

  103. Widdicombe J.H., Bastacky S.J., Wu D.X., Lee C.Y. 1997. Regulation of depth and composition of airway surface liquid. Eur. Respir. J. 10:2892–2897

    PubMed  CAS  Google Scholar 

  104. Widdicombe J.H., Widdicombe J.G. 1995. Regulation of human airway surface liquid. Respir Physiol 99:3–12

    PubMed  CAS  Google Scholar 

  105. Willumsen N.J., Boucher R.C. 1992. Intracellular pH and its relationship to regulation of ion transport in normal and cystic fibrosis human nasal epithelia. J. Physiol. 455:247–269

    PubMed  CAS  Google Scholar 

  106. Willumsen N.J., Davis C.W., Boucher R.C. 1989. Intracellular Cl activity and cellular Cl pathways in cultured human airway epithelium. Am. J. Physiol. 256:C1033–C1044

    PubMed  CAS  Google Scholar 

  107. Zippel R., Meyer P., Schubel F. 1965. E6ine Methode zur Messung der Wasserstoffionenkonzentration und ihre Ergebnisse an Schleimhautoberflächen in Nase und Mundrachen. Eur. Arch. Oto-Rhino-Laryng. 186:115–127

    Google Scholar 

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Acknowledgements

Many thanks to Sarah Inglis (Dundee, Scotland), Mauri Krouse (Stanford, California), and Terry Machen (Berkeley, California) for reading and commenting on the manuscript. The authors’ laboratories are supported by NIH HL071829.

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Fischer, H., Widdicombe, J.H. Mechanisms of Acid and Base Secretion by the Airway Epithelium. J Membrane Biol 211, 139–150 (2006). https://doi.org/10.1007/s00232-006-0861-0

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