Airway Wall Structure

  • Peter K. Jeffery
  • Mariusz J. Gizycki
  • Andrew V. Rogers


In man and other mammalian species, the upper and lower airways are lined by a continuous mucosal layer. It is the site at which immune responses are initiated by immuno-competent cells on recognition of foreign molecules, suitably processed by resident antigen- presenting cells (APC). In humans, subsequent exposure to the relevant allergen initiates immune reactions, which may become persistent. Immune reactions are designed as defense mechanisms that normally protect the body; however, inappropriate or misdirected responses may lead to damage of host tissues. Control is maintained by cell—cell signaling via the release of cytokines that have the potential to induce an allergic inflammatory response. At rest, approx 10,000 to 15,000 L of air, containing allergen and pollutants, moves daily over the nasal and tracheobronchial airway mucosal lining of the adult human lung. hi the upper respiratory tract and proximal conducting airways of the lung the air is sampled, conditioned, and rendered free of many irritants and allergens before reaching the respiratory portion of the lung. The function of the conducting airways, in many respects, depends on the branching pattern and the dynamic interaction of structural, immuno-competent, and neural elements. Changes in the composition and integrity of airway-wall structural components may alter its effectiveness. A prerequisite to understanding the pathogenesis of allergic inflammatory disorders is an appreciation of normal airway structure and function. The present chapter focuses on cells that comprise the normal structure of the airway wall of the lower respiratory tract and considers briefly the cellular and structural variations that occur in allergic disease, in particular, those that may lead to the process of airway-wall remodeling, a characteristic change in chronic asthma.


Airway Smooth Muscle Bronchial Smooth Muscle Airway Lumen Cellular Aspect Lamina Reticularis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Horsefield K (1974) The relation between structure and function in the airways of the lung. Br J Dis Chest 68: 145.CrossRefGoogle Scholar
  2. 2.
    Horsefield K (1981) The structure of the tracheobronchial tree. In: Scadding JG, Cumming G, Thurlbeck WM, eds. Respiratory Medicine. Heinemann, London, p. 54.Google Scholar
  3. 3.
    Evans MJ, Plopper CG (1988) The role of basal cells in adhesion of columnar epithelium to airway basement membrane. Am Rev Respir Dis 138: 481–483.PubMedCrossRefGoogle Scholar
  4. 4.
    Jeffery PK, Reid L (1975) New observations of rat airway epithelium: a quantitative electron microscopic study. J Anat 120: 295–320.PubMedGoogle Scholar
  5. 5.
    Lumsden AB, McLean A, Lamb D (1984) Goblet and Clara cells of human distal airways: evidence for smoking-induced changes in numbers. Thorax 39: 844–853.PubMedCrossRefGoogle Scholar
  6. 6.
    Jeffery PK (1983) Morphology of airway surface epithelial cells and glands. Am Rev Respir Dis 128:S 14–S20.Google Scholar
  7. 7.
    Jeffery PK (1978) The structure and function of the mucus-secreting cells of cat and goose airway epithelium. In: Porter R, ed. Respiratory Tract Mucus, 56th CIBA Foundation Symposium. Elsevier/Excerpta Med, Amsterdam, pp. 5–24.Google Scholar
  8. 8.
    Jeffery PK (1995) Microscopic structure of normal lung. In: Brewis RAL, Gibson GJ, Geddes GM, eds. Respiratory Medicine. 2nd Ed. Bailliere Tindall, London/Toronto, pp. 54–72.Google Scholar
  9. 9.
    Jeffery PK, Corrin B (1984) Structural analysis of the respiratory tract. In: Bienenstock J, ed. Immunology of the Lung. McGraw-Hill, New York, pp. 1–27.Google Scholar
  10. 10.
    Breeze RG, Wheeldon EB (1977) The cells of the pulmonary airways. Am Rev Respir Dis 116: 705–777.PubMedGoogle Scholar
  11. 11.
    McDermott MR, Befus AD, Bienenstock J (1982) The structural basis for immunity in the respiratory tract. Internat Rev Exp Path 23: 47–112.Google Scholar
  12. 12.
    Jeffery PK (1986) Innervation of airway epithelium. In: Kay AB, ed. Asthma: Clinical Pharmacology and Therapeutic Progress. Blackwell, Oxford, pp. 376–392.Google Scholar
  13. 13.
    Jeffery PK (1994) Innervation of the airway mucosa: structure, function and changes in airway disease. In: Goldie R, et al., eds. Immunopharmacology of Epithelial Barriers. Academic, London, pp. 85–118.Google Scholar
  14. 14.
    Sleigh HA (1977) The nature and action of respiratory tract cilia. In: Brain JD, et al., eds. Respiratory Defense Mechanisms, Part 1. Dekker, New York.Google Scholar
  15. 15.
    Pavia D, Lopez-Vidriero MT, Clarke SW (1987) Mediators and mucociliary clearance in asthma. Bull Eur Physiopathol Respir 23Suppl. 10: 89s–94s.Google Scholar
  16. 16.
    Mossberg B, Strandberg K, Phillipson K, Camner P (1976) Tracheobronchial clearance in bronchial asthma: response to beta-adrenoceptor stimulation. Scand J Respir Dis 57: 119–128.PubMedGoogle Scholar
  17. 17.
    Carlstedt I, Sheehan JK (1984) Macromolecular properties and polymeric structure of mucus glycoproteins. In: Nugent J, O’Connor M, eds. Mucus and Mucosa, Ciba Foundation Symposium 109. Pitman, Bath, pp. 157–172.CrossRefGoogle Scholar
  18. 18.
    Lamb D, Reid L (1968) Mitotic rates, goblet cell increase and histochemical changes in mucus in rat bronchial epithelium during exposure to SO2. J Pathol Bacteriol 96: 97–111.PubMedCrossRefGoogle Scholar
  19. 19.
    Jones R, Bolduc P, Reid L (1972) Protection of rat bronchial epithelium against tobacco smoke. Br Med J 2: 142–144.PubMedCrossRefGoogle Scholar
  20. 20.
    Jeffery PK, Reid L (1981) The effect of tobacco smoke with or without phenylmethyloxadiazole (PMO) on rat bronchial epithelium: a light and electron microscopic study. J Pathol 133: 341–359.PubMedCrossRefGoogle Scholar
  21. 21.
    Jeffery PK (1990) Tobacco smoke-induced lung disease. In: Cohen RD, Lewis B, Alberti KGMM, Denman AM, eds. The Metabolic and Molecular Basis of Acquired Disease. Balliere Tindall, London, pp. 466–495.Google Scholar
  22. 22.
    McDowell EM, Trump BF (1983) Conceptual review: histogenesis of preneoplastic and neoplastic lesions in tracheobronchial epithelium. Sury Synth Path Res 2: 235–279.Google Scholar
  23. 23.
    Ayers M, Jeffery PK (1982) Cell division and differentiation in the respiratory tract. In: Cumming G, Bonsignore G, eds. Cell Biology and the Lung. Plenum, New York, pp. 33–60.CrossRefGoogle Scholar
  24. 24.
    Jeffery PK, Ayers M, Rogers DF (1982) The mechanisms and control of bronchial mucous cell hyperplasia. Chest 815: 27S–29S.CrossRefGoogle Scholar
  25. 25.
    Ayers M, Jeffery PK (1988) Proliferation and differentiation in adult mammalian airway epithelium: a review. Eur Respir J 1: 58–80.PubMedGoogle Scholar
  26. 26.
    Ellefsen P, Tos M (1972) Goblet cells in the human trachea: quantitative studies of a pathological biopsy material. Arch Otolaryngol 95: 547–555.PubMedCrossRefGoogle Scholar
  27. 27.
    Jeffery PK, Wardlaw A, Nelson FC, Collins JV, Kay AB (1989) Bronchial biopsies in asthma: an ultra-structural quantification study and correlation with hyperreactivity. Am Rev Respir Dis 140: 1745–1753.PubMedCrossRefGoogle Scholar
  28. 28.
    Rogers AV, Dewar A, Corrin B, Jeffery PK (1993) Identification of serous-like cells in the surface epithelium of human bronchioles. Eur Respir J 6: 498–504.PubMedGoogle Scholar
  29. 29.
    Willems LNA, Kramps JA, Jeffery PK, Dijkman JH (1988) Detection of antileukoprotease in the developing foetal lung. Thorax 43: 784–786.PubMedCrossRefGoogle Scholar
  30. 30.
    Niden AH (1980) Bronchiolar and large alveolar cell in pulmonary phospholipid metabolism. Science 158: 1323–1324.CrossRefGoogle Scholar
  31. 31.
    Gil J, Weibel E (1971) Extracellular lining of bronchioles after perfusion-fixation of rat lungs for electron microscopy. Anat Rec 169: 185–200.PubMedCrossRefGoogle Scholar
  32. 32.
    Sallenave JM, Silva A, Marsden ME, Ryle AP (1993) Secretion of mucus proteinase inhibitor and alefin by Clara cell and type II pneumocyte cell lines. Am J Resp Cell Mol Biol 8: 126–133.Google Scholar
  33. 33.
    Evans MJ, Cabral-Anderson LJ, Freeman G (1978) Role of the Clara cell in renewal of bronchiolar epithelium. Lab Invest 38: 648–655.PubMedGoogle Scholar
  34. 34.
    Lauweryns JM, Cokelaere M, Theunynck P (1972) Neuro-epithelial bodies in the respiratory mucosa of various mammals. Z Zellforsch Mikrosk Anatomy 135: 569–592.CrossRefGoogle Scholar
  35. 35.
    Lauweryns JM, De Bock V, Verhofstad AAJ, Steinbusch HWM (1982) Immunohistochemical localization of serotonin in intrapulmonary neuro-epithelial bodies. Cell Tiss Res 226: 215–223.Google Scholar
  36. 36.
    Wharton J, Polak JM, Bloom SR, Ghatei MA, Solcia E, Brown MR, Pearse AG (1978) Bombesin-like immunoreactivity in the lung. Nature 273: 769–770.PubMedCrossRefGoogle Scholar
  37. 37.
    Schlegel R, Banko-Schlegel S, Pinkus GS (1980) Immunohistochemical localization of keratin in normal human tissues. Lab Invest 42: 91–96.PubMedGoogle Scholar
  38. 38.
    Blenkinsopp WK (1967) Proliferation of respiratory tract epithelium in the rat. Exp Cell Res 46: 144–154.PubMedCrossRefGoogle Scholar
  39. 39.
    Bolduc P, Reid L (1978) The effect of isoprenaline and pilocarpine on mitotic index and goblet cell number in rat respiratory epithelium. Br J Exp Pathol 59: 311–318.PubMedGoogle Scholar
  40. 40.
    Erjefalt JS, Erjefalt I, Sundler F, Persson CGA (1995) In vivo restitution of airway epithelium. Cell Tissue Res 281: 305–316.PubMedCrossRefGoogle Scholar
  41. 41.
    Beasley R, Roche W, Roberts JA, Holgate ST (1989) Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis 139: 806–817.PubMedGoogle Scholar
  42. 42.
    Montefort S, Roberts JA, Beasley R, Holgate ST, Roche WR (1992) The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects. Thorax 47: 499–503.PubMedCrossRefGoogle Scholar
  43. 43.
    Lamb D, Lumsden A (1982) Infra-epithelial mast cells in human airway epithelium: evidence for smoking-induced changes in their frequency. Thorax 37: 334–342.PubMedCrossRefGoogle Scholar
  44. 44.
    Irani AA, Bradford TR, Kepley CL, Schechter NM, Schwartz LB (1989) Detection of MC-T and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and antichymase antibodies. J Histochem Cytochem 37: 1509–1515.PubMedCrossRefGoogle Scholar
  45. 45.
    Razin E, Ihle JW, Seldin D, et al. (1984) Interleukin 3: a differentiation and growth factor for the mouse mast cell that contains chondroitin sulfate E proteoglycan. J Immunol 132: 1479–1486.Google Scholar
  46. 46.
    Irani AA, Schechter NM, Craig SS, Deblois G, Schwartz LB (1986) Two types of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci USA 83: 4464–4468.PubMedCrossRefGoogle Scholar
  47. 47.
    Kent JF (1966) Distribution and fine structure of globular leukocytes in respiratory and digestive tracts of the laboratory rat. Anat Rec 156: 439–454.PubMedCrossRefGoogle Scholar
  48. 48.
    Jeffery PK, Reid L (1977) The ultrastructure of the airway lining and its development. In: Hodson WA, ed. The Development of the Lung. Marcel Dekker, New York, pp. 87–134.Google Scholar
  49. 49.
    Fournier M, Lebargy F, Le Roy Ladurie F, Lenormand E, Pariente R (1989) Intraepithelial T-lymphocyte subsets in the airways of normal subjects and of patients with chronic bronchitis. Am Rev Respir Dis 140: 737–742.Google Scholar
  50. 50.
    Corrigan CJ, Hartnell A, Kay AB (1988) T lymphocyte activation in acute severe asthma. Lancet, Vol 1: 1129–1131.Google Scholar
  51. 51.
    Robinson DS, Hamid Q, Sun-Ying, Tsicopoulos A, Barhani J, Bentley AM, Corrigan CJ, Durham SR, Kay AB (1992) Predominant Th2-type bronchoalveolar lavage T lymphocyte popularity in atopic asthma. N Engl J Med 326: 298–304.Google Scholar
  52. 52.
    De Carlo Massaro G (1989) Nonciliated bronchoepithelial (Clara) cells. In: Massaro D, ed. Lung Cell Biology. Markel Dekker, New York, pp. 81–107.Google Scholar
  53. 53.
    O’Shaughnessy TC, Ansari TW, Barnes NC, Jeffery PK (1995) T-cell markers in smokers’ chronic bronchitis with and without airflow obstruction. Eur Respir J 8 (Suppl. 19): 493s.Google Scholar
  54. 54.
    Holt PG (1993) Regulation of antigen-presenting cell function(s) in lung and airway tissues. Eur Respir J 6: 120–129.PubMedGoogle Scholar
  55. 55.
    Holt PG, Schon-Hegrad MA, Phillips MJ, McMenamin PG (1989) Ia-positive dendritic cells form a tightly meshed network within the human airway epithelium. Clin Exp Allergy 19: 597–601.PubMedCrossRefGoogle Scholar
  56. 56.
    Holt PG, Schon-Hegrad MA, Oliver J, Holt BJ, McMenamin PG (1990) A contiguous network of dendritic antigen-presenting cells within the respiratory epithelium. Int Arch Allergy Appl Iinmunl 91: 155–159.CrossRefGoogle Scholar
  57. 57.
    Caux C, Dezutter-Dambuyant C, Scmitt D, Banchereau J (1992) GM-CSF and TNF-a cooperate in the generation of dendritic Langerhans cells. Nature 360: 258–261.PubMedCrossRefGoogle Scholar
  58. 58.
    Kasinrerk W, Baumruker T, Majdic O, Knapp W, Stockinger H (1993) CD1 molecule expression on human monocytes induced by GM-CSF. J Immunol 150: 579–584.PubMedGoogle Scholar
  59. 59.
    Steinbach F, Krause B, Thiele B (1995) Monocyte derived dendritic cells ( MODC) present phenotype and functional activities of Langerhans cells/dendritic cells. Adv Exp Med Biol 378: 151–153.Google Scholar
  60. 60.
    Xu H, Kramer M, Spengel HP, Peters JH (1995) Dendritic cells differentiated from human monocytes through a combination of IL-4, GM-CSF and IFN-i exhibit phenotype and function of blood dendritic cells. Adv Exp Med Biol 378: 75–78.Google Scholar
  61. 61.
    Peters JH, Ruppert J, Gieseler RK, Najar HM, Xu H (1991) Differentiation of human monocytes into CD14 negative accessory cells: do dendritic cells derive from the monocyte lineage? Pathobiology 59: 122–126.PubMedCrossRefGoogle Scholar
  62. 62.
    Reid CD, Stackpoole A, Meager A, Tikarpae J (1992) Interaction of TNF with GM-CSF and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow. J Immunol 149: 2681–2688.PubMedGoogle Scholar
  63. 63.
    Rossi G, Heveker N, Thiele B, Gelderblom H, Steinbach F (1992) Development of Langerhans cell phenotype from peripheral blood monocytes. Immunol Lett 31: 189–197.PubMedCrossRefGoogle Scholar
  64. 64.
    Peters JH, Ruhl S, Friedrichs D (1987) Veiled accessory cells deduced from monocytes. Immunobiology 176: 154–166.PubMedCrossRefGoogle Scholar
  65. 65.
    Steinbach F, Thiele B (1993) Monocyte-derived Langerhans cells from different species-morphological and functional characterization. Adv Exp Med Biol 239: 213–218.CrossRefGoogle Scholar
  66. 66.
    Peters JH, Gieseler R, Thiele B, Steinbach F (1996) Dendritic cells: from ontogenetic orphans to myelomonocytic descendants. Immunol Today 17: 273–278.PubMedCrossRefGoogle Scholar
  67. 67.
    Glanville AR, Tazelaar HD, Therodore J, et al. (1989) The distribution of mhc class I and II antigens on bronchial epithelium. Am Rev Respir Dis 139: 330–334.PubMedCrossRefGoogle Scholar
  68. 68.
    Natali PC, De Martino C, Quarawta V (1981) Expression of Ia-like antigens in normal human non-lymphoid tissues. Transplantation 31: 75–78.Google Scholar
  69. 69.
    Dunnill MS (1960) The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol 13: 27–33.PubMedCrossRefGoogle Scholar
  70. 70.
    Laitinen LA, Heino M, Laitinen A, Kava T, Haahtela T (1985) Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis 131: 599–606.PubMedGoogle Scholar
  71. 71.
    Ilowite JS, Bennett WD, Sheetz MS, Groth ML, Nierman DM (1989) Permeability of the bronchial mucosa to 99mTc DTPA in asthma. Am Rev Respir Dis 139: 1139–1143.PubMedGoogle Scholar
  72. 72.
    Godfrey RWA, Severs NJ, Jeffery PK (1992) Freeze-fracture morphology and quantification of human bronchial epithelial tight junctions. Am J Respir Cell Molec Biol 6: 453–458.Google Scholar
  73. 73.
    Schneeberger EE, Lynch RD (1992) Structure, function, and regulation of cellular tight junctions. J Appl Phys 262: L647–L661.Google Scholar
  74. 74.
    Faff O, Mitreiter R, Muckter H, Ben-Shaul Y, Bacher A (1988) Rapid formation of tight junctions in HT 29 human adenocarcinoma cells by hypertonic salt solutions. Exp Cell Res 177: 60–72.PubMedCrossRefGoogle Scholar
  75. 75.
    Madara JL (1988) Tight junction dynamics: is paracellular transport regulated. Cell 53: 497–498.PubMedCrossRefGoogle Scholar
  76. 76.
    Elia C, Bucca C, Rolla G, Scappaticci E, Cantino D (1988) A freeze-fracture study of tight junctions in human bronchial epithelium in normal, bronchitic and asthmatic subjects. J Submic Cytol Pathol 20: 509–517.Google Scholar
  77. 77.
    Ohashi Y, Montojima S, Fukuda T, Makino S (1992) Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma. Am Rev Respir Dis 145: 1469–1476.PubMedGoogle Scholar
  78. 78.
    Lake FR, Ward LD, Simpson PJ, Thompson PJ (1991) The group III allergens from house dust mite Dermatophagoides pteronyssinus is a trypsin-like enzyme. Immunobiology 87: 1035–1042.Google Scholar
  79. 79.
    Herbert CA, King CM, Ring PC, Holgate ST, Stewart GA, Thompson PJ (1995) Augmentation of permeability in the bronchial epithelium by the house dust mite allergen, Der pl. Am J Respir Cell Mol Biol 129: 369–378.Google Scholar
  80. 80.
    Takeichi M (1996) Cadherins: a molecular family important in selective cell-cell adhesion. Annu Rev Biochem 59: 237–252.CrossRefGoogle Scholar
  81. 81.
    Trigg CJ, Manolitsas ND, Wang J, Calderon MA, McAulay A, Jordan SE, Herdman MJ, Jhalli N, Duddle JM, Hamilton SA, Devalia JL, Davies RJ (1994) Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. Am J Respir Crit Care Med 150: 17–22.PubMedGoogle Scholar
  82. 82.
    Gosset P, Tillie-Leblond I, Janin A, Marquette CH, Copin MC, Wallaert B, Tonnel AB (1994) Increased expression of ELAM-1, ICAM-1, and VCAM-1 on bronchial biopsies from allergic asthmatic patients. Ann N Y Acad Sci 725: 163–172.PubMedGoogle Scholar
  83. 83.
    Wegner CD, Gundel RH, Reilly P, Haynes N, Letts LG, Rothlein R (1990) Intercellular adhesion molecule-1 [ICAM-1] in the pathogenesis of asthma. Science 247: 456–459.PubMedCrossRefGoogle Scholar
  84. 84.
    Kleinman HK, Graf J, Iwamoto Y, Kitten GT, Ogle RC, Sasaki M, Yamada Y, Martin GR, LuckenbillEdds L (1987) Role of basement membranes in cell differentiation. Ann N Y Acad Sci 513: 134–145.PubMedCrossRefGoogle Scholar
  85. 85.
    Merker HJ (1994) Morphology of the basement membrane. Microsc Res Tech 28: 95–124.PubMedCrossRefGoogle Scholar
  86. 86.
    Timpl R, Dziadek M (1986) Structure, development, and molecular biology of basement membranes. Int Rev Exp Pathol 29: 1–112.PubMedGoogle Scholar
  87. 87.
    Scittny JC, Yurchenco PD (1989) Basement membranes: molecular organisation and function in development and disease. Curr Opin Cell Biol 1: 983–988.CrossRefGoogle Scholar
  88. 88.
    Ozawa M, Sato M, Muramatsu T (1983) Basement membrane glycoprotein laminin is an agglutin. J Biochem 94: 479–485.PubMedGoogle Scholar
  89. 89.
    Laurie GW, Bing JT, Kleinman HK, Hassell JR, Aumailley M, Martin GR, Feldmann RJ (1986) Localization of binding sites for laminin, heparan sulfate proteoglycan and fibronectin on basement membrane (type IV) collagen. J Mol Biol 189: 205–216.PubMedCrossRefGoogle Scholar
  90. 90.
    Abrahamson DR (1986) Recent studies on the structure and pathology of basement membranes. J Pathol 149: 257–278.PubMedCrossRefGoogle Scholar
  91. 91.
    Timpl R (1989) Structure and biological activity of basement membrane proteins. Eur J Biochem 180: 487–502.PubMedCrossRefGoogle Scholar
  92. 92.
    Chung AE, Durkin ME (1990) Entactin: structure and function. Am J Resp Cell Mol Biol 3: 275–282.Google Scholar
  93. 93.
    Martin GR, Timpl R (1987) Laminin and other basement membrane components. Ann Rev Cell Biol 3: 57–85.PubMedCrossRefGoogle Scholar
  94. 94.
    Dziadek M (1995) Role of laminin-nidogen complexes in basement membrane formation during embryonic development. Experientia 51: 901–913.PubMedCrossRefGoogle Scholar
  95. 95.
    Timpl R (1993) Proteoglycans of basement membrane. Experientia 49: 417–428.PubMedCrossRefGoogle Scholar
  96. 96.
    Kuhn K (1995) Basement membrane (type IV) collagen. Matrix Biology 14: 439–445 (abstract).PubMedCrossRefGoogle Scholar
  97. 97.
    Crepea SB, Harman JW (1955) The pathology of bronchial asthma. I. The significance of membrane changes in asthmatic and non-allergic pulmonary disease. J Allergy 26: 453–460.Google Scholar
  98. 98.
    Roche WR, Beasley R, Williams JH, Holgate ST (1989) Subepithelial fibrosis in the bronchi of asthmatics. Lancet i: 520–523.Google Scholar
  99. 99.
    Lambert RK (1991) Role of bronchial basement membrane in airway collapse. J Appl Physiol 71: 666–673.PubMedGoogle Scholar
  100. 100.
    Rennard SI, Bitterman PB, Crystal RG (1984) Pathogenesis of the granulomatous lung disease. IV. Mechanisms of fibrosis. Am J Resp Crit Care Med 130: 492–496.Google Scholar
  101. 101.
    Stetler-Stevenson WG (1996) Dynamics of matrix turnover during pathologic remodelling of the extra-cellular matrix. Am J Pathol 148: 1345–1350.PubMedGoogle Scholar
  102. 102.
    Lin LL, Lin AY, DeWitt DL (1992) Interleukin-1 alpha induces the accumulation of cytosolic phospholipase A2 and the release of prostaglandin E2 in human fibroblasts. J Biol Chem 267: 23451–23454.PubMedGoogle Scholar
  103. 103.
    Dayer JM, Beutler B, Cerami A (1985) Cachectin/tumor necrosis factor stimulates collagenases and prostaglandin E production by human synovial cells and dermal fibroblasts. J Exp Med 162: 2163–2166.Google Scholar
  104. 104.
    Snijdewint FGM, Kalinsky P, Wierenga EA, Bos JD, Kapsenberg ML (1993) Prostaglandin E2 differentially modulates cytokine secretion profiles of human T-helper lymphocytes. J Immunol 150: 5321–5329.PubMedGoogle Scholar
  105. 105.
    Roper RL, Conrad DH, Brown DM, Warner GL, Phipps RP (1990) Prostaglandin E2 promotes IL-4 induced IgE and IgG1 synthesis. J Immunol 145: 2644–2651.PubMedGoogle Scholar
  106. 106.
    Betz M, Fox BS (1991) Prostaglandin E2 inhibits production of Thl lymphokines but not of Th2 lymphokines. J Immunol 146: 108–113.PubMedGoogle Scholar
  107. 107.
    Lukacs NW, Chensue SW, Smith RE, et al. (1994) Production of monocyte chemoattractant-1 (MCP-1) and macrophage inflammatory protein (M1P-1a) by inflammatory granuloma fibroblasts. Am J Pathol 144: 711–718.PubMedGoogle Scholar
  108. 108.
    Stiles AD, D’Ercole AJ (1990) The insulin-like growth factors and the lung. Am J Resp Cell Mol Biol 3: 93–100.Google Scholar
  109. 109.
    Zucali JR, Dinarello CA, Oblon DJ, Gross MA, Anderson L, Weiner RS (1986) Interleukin-1 stimulates fibroblasts to produce GM-CSF. J Clin Invest 77: 1857–1863.PubMedCrossRefGoogle Scholar
  110. 110.
    Vancheri C, Ohtoshi T, et al. (1991) Neutrophil differentiation by human upper airway fibroblast-derived granulocyte/macrophage colony stimulating factor ( GM-CSF ). Am J Resp Cell Mol Biol 4: 11–17.Google Scholar
  111. 111.
    Rubbia-Brandt L, Sappino A, Gabbiani G (1991) Locally applied GM-CSF induces accumulation of alpha-smooth muscle actin containing fibroblasts. Virchows Arch B Cell Pathol 60: 73–82.CrossRefGoogle Scholar
  112. 112.
    Franke WW, Schinko W (1969) Nuclear shape in muscle cells. J Cell Biol 42: 326–331.PubMedCrossRefGoogle Scholar
  113. 113.
    Kapanci Y, Assimacopoulos A, Irle C, Zwahlen A, Gabbiani G (1974) Contractile interstitial cells in pulmonary alveolar septa: A possible role of ventilation/perfusion ratio? J Cell Biol 60:375–392.Google Scholar
  114. 114.
    Brewster CEP, Howarth PH, Djukanovic R, Wilson J, Holgate ST, Roche WR (1990) Myofibroblasts and subepithelial fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 3: 507–511.PubMedGoogle Scholar
  115. 115.
    Gizycki MJ, Adelroth E, Rogers AV, O’Byrne PM, Jeffery PK (1997) Myofibroblast involvement in the allergen induced late response in mild atopic asthma. Am J Respir Crit Care Med 16: 664–673.Google Scholar
  116. 116.
    Skalli O, Schurch W, Seemayer T, Lagace R, Montandon D, Pittet B, Gabbiani G (1989) Myofibroblast from diverse pathologic settings are heterogenous in their content of actin isoforms and intermediate filament proteins. Lab Invest 60: 275–285.PubMedGoogle Scholar
  117. 117.
    Schmitt-Graff A, Desmouliere A, Gabbiani G (1994) Heterogeneity of myofibroblast phenotypic features: an example of fibroblastic cell plasticity. Virchows Archiv 425: 3–24.PubMedCrossRefGoogle Scholar
  118. 118.
    Sappino AP, Schurch W, Gabbiani G (1990) Differentiation repertoire of fibroblast cells: expression of cytoskeletal proteins as markers of phenotypic modulation. Lab Invest 63: 144–161.PubMedGoogle Scholar
  119. 119.
    Adler KB, Callahan LM, Evans JN (1986) Cellular alterations in the alveolar wall in bleomycin-induced lung fibrosis in rats: An ultrastructural morphometric study. Am J Resp Crit Care Med 133: 1043–1048.Google Scholar
  120. 120.
    Kapanci Y, Burgan S, Pietra GG, Conne B, Gabbiani G (1990) Modulation of actin isoforms expression in alveolar myofibroblasts (contractile interstitial cells) during pulmonary hypertension. Am J Pathol 136: 881–889.PubMedGoogle Scholar
  121. 121.
    Mitchell J, Woodcock-Mitchell J, Reynolds S, Low RB, Leslie KO, Adler K, Gabbiani G, Omar S (1989) Alpha smooth muscle actin in parenchymal cells of bleomycin-injured rat lung. Lab Invest 60: 643–650.PubMedGoogle Scholar
  122. 122.
    Gabbiani G, Lous ML, Bailey AJ, Bazin S, Delaunay A (1976) Collagen and myofibroblasts of granulation tissue. A chemical, ultrastructural and immunologic study. Virchows Arch B Cell Pathol 21: 133–145.Google Scholar
  123. 123.
    Gabbiani G, Chaponnier C, Huttner I (1978) Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. J Cell Biol 76: 561–568.PubMedCrossRefGoogle Scholar
  124. 124.
    Darby I, Skalli O, Gabbiani G (1990) a-Smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest 63: 21–29.Google Scholar
  125. 125.
    Carroll N, Elliot A, Morton A, James A (1993) The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 147: 405–410.PubMedGoogle Scholar
  126. 126.
    Severs NJ, Robenek H (1992) Constituents of the arterial wall and atherosclerotic plaque: an introduction to atherosclerosis. In: Cell Interactions in Atherosclerosis. Robenek H, Severs NJ, eds. CRC Press, Boca Raton, pp. 1–49.Google Scholar
  127. 127.
    Campbell GR, Chamley-Campbell JH, Burnstock G (1981) Differentiation and phenotypic modulation of arterial smooth muscle. In: Schwartz CJ, Werthessen NT, Wolf S, eds. Structure and Function of Circulation, vol. 3. Plenum, New York, pp. 357–399.CrossRefGoogle Scholar
  128. 128.
    Thyberg J, Nilsson J, Palmberg L, Sjolund M (1985) Adult human arterial smooth muscle cells in primary culture: modulation from contractile to synthetic phenotype. Cell Tissue Res 239: 501–513.CrossRefGoogle Scholar
  129. 129.
    Okamoto E, Imataka K, Fujii J, Kuro M, Nakaharak K, Nishimura H, Yazaki Y, Nagai R (1992) Heterogeneity in smooth muscle cell populations in neointimas and the media of post-stenotic dilatation of rabbit carotid artery. Biochem Biophys Res Commun 185: 459–464.PubMedCrossRefGoogle Scholar
  130. 130.
    Kelleher MD, Schneider SD, Naureckas ET, Abe Mk, Jain M, Solvay J, Hershenson MB (1994) Responsiveness of bovine tracheal smooth muscle cells to various mitogens. Am J Resp Crit Care Med 149: A304 (abstract).Google Scholar
  131. 131.
    Hirst SJ, Barnes PJ, Twort CHC (1996) PDGF receptor expression and differential proliferation induced by PDGF isoforms in human cultured bronchial smooth muscle. Am J Physiol 270: L415–428.PubMedGoogle Scholar
  132. 132.
    Hirst SJ, Barnes PJ, Twort CHC (1994) Proliferation of human and rabbit smooth muscle in culture by platelet-derived growth factor isoforms. Am J Resp Crit Care Med 149: A303 (abstract).Google Scholar
  133. 133.
    Black PN, Young PG, Scott L, Merrolees MJ, Skinner SJM (1994) Is Transforming growth factor-beta an autocrine growth factor for airway smooth muscle? Am J Resp Crit Care Med 149: A302 (abstract).Google Scholar
  134. 134.
    Amento EP, Ehsani N, Palmer H, Libby P (1991) Cytokines and growth factors positively and negatively regulate interstitial collagen synthesis gene expression in human vascular smooth muscle cells. Arteriosclerosis Thromb 11: 1223–1230.CrossRefGoogle Scholar
  135. 135.
    Brown JK, Tyler CL, Jones CA, Ruoss SJ, Hartmann T, Caughey GH (1995) Tryptase, the dominant secretory granular protein in human mast cells, is a potent mitogen for cultured dog tracheal smooth muscle cells. Am J Resp Cell Mol Biol 13: 227–236.Google Scholar
  136. 136.
    Rennick RE, Connat J-L, Burnstock G, Rothery S, Severs NJ, Green CR (1993) Expression of connexin 43 gap junctions between cultured vascular smooth muscle cells is dependent upon phenotype. Cell Tissue Res 271: 323–332.PubMedCrossRefGoogle Scholar
  137. 137.
    Skalli O, Pelte MF, Peclet MC, Gabbiani G, Gugliotta P, Bussolati G, Ravazzola M, Orci L (1989) Alpha smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous boundles of pericytes. J Histochem Cytochem 37: 315.PubMedCrossRefGoogle Scholar
  138. 138.
    Shepro D, Morel NML (1993) Pericyte physiology. FASEB J 7: 1031–1038.PubMedGoogle Scholar
  139. 139.
    Diaz-Flores L, Gutierrez R, Varela H, Rencel N, Valladares F (1991) Microvascular pericytes: a review of their morphological and functional characteristics. Histol Histopath 6: 269–286.Google Scholar
  140. 140.
    Charan NB, Baile EM, Paré PD (1997) Bronchial vascular congestion and angiogenesis. Eur Respir J 10: 1173–1180.PubMedCrossRefGoogle Scholar
  141. 141.
    Hislop A, Reid L (1976) New findings in pulmonary arteries of rats with hypoxia-induced hypertension. Br J Exp Path 57: 542–554.Google Scholar
  142. 142.
    Langlebeb D, Jones RC, Aronovitz MJ, Hill NS, Ou L-C, Reid LM (1987) Pulmonary artery structural changes in two colonies of rats with different sensitivity to chronic hypoxia. Am J Pathol 1128: 61–66.Google Scholar
  143. 143.
    Meyrick B, Reid L (1978) The effect of continued hypoxia on rat pulmonary arterial circulation: an ultrastructural study. Lab Invest 38: 188–192.PubMedGoogle Scholar
  144. 144.
    Sundberg C, Ivarsson M, Rubin K (1996) Pericytes as collagen-producing cells in excessive dermal scarring. Lab Invest 74: 452–466.PubMedGoogle Scholar
  145. 145.
    Miller (1937).Google Scholar
  146. 146.
    Dunnill MS, Massarella GR, Anderson JA (1969) A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis, and in emphysema. Thorax 24: 176–179.PubMedCrossRefGoogle Scholar
  147. 147.
    Jeffery PK (1992) Pathology of asthma. Br Med Bull 48: 23–39.PubMedGoogle Scholar
  148. 148.
    Heard BE, Hossain S (1973) Hyperplasia of bronchial muscle in asthma. J Pathol 110: 319–331.CrossRefGoogle Scholar
  149. 149.
    Ebina M, Takahashi T, Chiba T, Motomiya M (1993) Cellular hypertrophy and hyperplasia of airway smooth muscle underlying bronchial asthma. Am J Resp Crit Care Med 148: 720–726.CrossRefGoogle Scholar
  150. 150.
    Gabella G (1994) Anatomy of airways smooth muscle. In: Reabum D, Giembycz MA, eds. Airways Smooth Muscle: Structure, Innervation and Neurotransmission. Birkhauser Verlag, Basel, pp. 1–27.Google Scholar
  151. 151.
    Daniel EE, Triggle DJ (1993) Structure and function of airway smooth muscle. In: Middleton E Jr, Busse WW, Ellis EF, Reed CR, Yunginger JW, eds. Allergy: Principles and Practice. Mosby Year Book Co., St. Louis, MO, pp. 629–649.Google Scholar
  152. 152.
    Janssen L, Daniel EE (1994) Myogenic control of airways smooth muscle and cell-to-cell coupling. In: Raeburn D, Giembycz MA, eds. Airways Smooth Muscle: Development, and Regulation of Contractility. Birkhauser Verlag, Basel, pp. 101–136.CrossRefGoogle Scholar
  153. 153.
    Laitinen A, Laitinen LA, Moss R, Widdicombe JG (1989) Organisation and structure of the tracheal and bronchial blood vessels in the dog. J Anat 165: 133–140.PubMedGoogle Scholar
  154. 154.
    Laitinen LA, Robinson NP, Laitinen A, Widdicombe JG (1986) Relationship between tracheal mucosal thickness and vascular resistance in dogs. J Appl Physiol 61: 2186–2194.PubMedGoogle Scholar
  155. 155.
    Widdicombe J (1993) New perspectives on basic mechanisms in lung disease: 4. Why are the airways so vascular? Thorax 48: 290–295.PubMedCrossRefGoogle Scholar
  156. 156.
    Laitinen LA, Laitinen A (1992) The bronchial circulation: Histology and electron microscopy. In: Butler J, ed. The Bronchial Circulation. Dekker, New York, pp. 79–98.Google Scholar
  157. 157.
    Laitinen LA, Laitinen A, Widdicombe J (1987) Effects of inflammatory and other mediators on airway vascular beds. Am Rev Respir Dis 135: S67–S70.PubMedGoogle Scholar
  158. Lundberg JM, Lundblad C, Martling C, Saria A, St. Jame P, Anggard A (1987) Coexistence of multiple peptides and classic transmitters in airway neurons: functional and pathophysiologic aspects. Am Rev Respir Dis 136:S16–S22.Google Scholar
  159. 159.
    Lundblad L (1984) Protective reflexes and vascular beds in the nasal mucosa elicited by activation of capsaicin sensitive substance P immunoreactive trigeminal neurons. Acta Physiol Scand (Suppl)529: 1–42.Google Scholar
  160. 160.
    Deffebach ME, Salonen RO, Webber SE, Widdicombe JG (1991) Cold and hyperosmolar fluids in canine trachea: vascular and smooth muscle tone and albumin flux. J Appl Physiol 71: 50–59.PubMedGoogle Scholar
  161. 161.
    Salonen RO, Webber SE, Deffebach ME, Widdicombe JG (1991) Tracheal vascular and smooth muscle responses to air temperature and humidity in dogs. J Appl Physiol 71: 50–59.PubMedGoogle Scholar
  162. 162.
    McFadden ERJ (1990) Hypothesis: exercise-induced asthma as a vascular phenomenon. Lancet, 335: 880–883.PubMedCrossRefGoogle Scholar
  163. 163.
    Cauna N (1982) Blood and nerve supply of the nasal lining. In: Proctor DE, Anderson ID, eds. The Nose: Upper Airway Physiology and the Atmospheric Environment. Elsevier Biomedical, Amsterdam, pp. 45–69.Google Scholar
  164. 164.
    McDonald DM (1990) The ultrastructure and permeability of tracheobronchial blood vessels in health and disease. Eur Respir J 3: 572–855.Google Scholar
  165. 165.
    Cole P (1988) Nasal airflow resistance. In: Mathew OP, Sant’Ambrogio G, eds. Respiratory Function of the Upper Airway. Dekker, New York, pp. 391–414.Google Scholar
  166. 166.
    Baffle EM, Sotres-Vega A, Pare PD (1994) Airway blood flow and bronchovascular congestion in sheep. Eur Respir J 7: 1300–1307.CrossRefGoogle Scholar
  167. 167.
    Schleimer RP, Benenati SV, Friedman B, Bochner BS (1991) Do cytokines play a role in leukocyte recruitment and activation in the lungs? Am Rev Respir Dis 143: 1169–1174.PubMedGoogle Scholar
  168. 168.
    Schleimer, Sterbinsky, Saiser, Bickel, Klunk, Tomoika, Newman, Luscinskas, Gimbrone, McIntyre, Bochner, (1992) IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelial cells. J Immunol 148: 1048–1092.Google Scholar
  169. 169.
    Jeffery PK (1982) Bronchial mucosa and its innervation. In: Cumming G, Bonsignore G, eds. Cell Biology and the Lung Plenum, New York, pp. 1–32.Google Scholar
  170. 170.
    Shipperbottom CA (1988) Histochemical studies of the autonomic innervation of normal and diseased human lung. Thesis submitted to the University of London for MPhil degree.Google Scholar
  171. 171.
    Uddman R, Sundler F (1987) Neuropeptides in the airways. Am Rev Respir Dis 136: S3–S8.PubMedCrossRefGoogle Scholar
  172. 172.
    Dusser DJ, Umeno E, Graf PD, Djokic T, Borson DB, Nadel JA (1988) Airway neutral endopeptidaselike enzyme modulates tachykinin-induced bronchoconstriction in vivo. J Appl Physiol 65: 2585–2591.PubMedGoogle Scholar
  173. 173.
    Dusser DJ, Djokic TD, Borson DB, Nadel JA (1989) Cigarette smoke induces bronchoconstrictor hyper-responsiveness to substance P and inactivates airway neutral endopeptidase in the guinea pig lung. Possible role of free radicals. J Clin Invest 84: 900–906.Google Scholar
  174. 174.
    Barnes PJ (1992) Modulation of neurotransmission in airways. Physiol Rev 72: 699–729.PubMedGoogle Scholar
  175. 175.
    Jeffery PK, Reid L (1973) Intraepithelial nerves in normal rat airways: a quantitative electron microscopic study. J Anat 114: 33–45.Google Scholar
  176. 176.
    Hung KS (1976) Fine structure of tracheobronchial epithelial nerves of the cat. Anat Rec 185: 85–91.PubMedCrossRefGoogle Scholar
  177. 177.
    Das RM, Jeffery PK, Widdicombe JG (1978) The epithelial innervation of the lower respiratory tract of the cat. J Anat 126: 123–131.PubMedGoogle Scholar
  178. 178.
    Fillenz M, Woods MJ (1970) Sensory innervation of airways. In: Porter R, ed. Breathing: Hering-Breuer Centenary Symposium. Ciba Foundation Symp., Amsterdam, pp. 101–109.CrossRefGoogle Scholar
  179. 179.
    Boucher RC, Johnson J, Inoue S, Hulbert W, Hogg JC (1980) The effect of cigarette smoking on the permeability of guinea pig airways. Lab Invest 43: 94–100.PubMedGoogle Scholar
  180. 180.
    Cook RD, King RS (1969) A neurite-receptor complex in the avian lung: electron microscopical observations. Experientia 25: 1162–1164.PubMedCrossRefGoogle Scholar
  181. 181.
    Cook RD, King RS (1969) Nerves of the avian lung: electron microscopy. J Anat 105: 202–203.PubMedGoogle Scholar
  182. 182.
    King AS, McLelland J, Cook RD, King DZ, Walsh C (1974) The ultrastructure of afferent nerve endings in the avian lung. Resp Physiol 22: 21–40.CrossRefGoogle Scholar
  183. 183.
    Walsh C, McLelland J (1974) The ultrastructure of the avian extrapulmonary respiratory epithelium. Acta Anat 89: 412–422.PubMedCrossRefGoogle Scholar
  184. 184.
    Phipps RJ, Richardson PS, Corfield A, Gallagher JT, Jeffery PK, Kent PW, Passatore M (1977) A physiological biochemical and histological study of goose tracheal mucin and its secretion. Phil Trans Roy Soc (Lond) B, 279: 513–543.CrossRefGoogle Scholar
  185. 185.
    Rhodin J (1966) The ciliated cells. Ultrastructure and function of the human tracheal mucosa. Am Rev Respir Dis 93: 1–15.PubMedGoogle Scholar
  186. 186.
    Lauweryns JM, Peuskens JC, Cokelaere M (1970) Argyrophil, fluorescent and granulated (peptide and amine producing?) AFG cells in human infant bronchial mucosa. Light and electron microscopic studies. Life Sci 9: 1417–1429.Google Scholar
  187. 187.
    Laitinen A (1985) Ultrastructural organization of intraepithelial nerves in the human airway tract. Thorax 40: 488–492.PubMedCrossRefGoogle Scholar
  188. 188.
    Hulbert WC, Walker DC, Jackson A, Hogg JC (1981) Airway permeability to horseradish peroxidase in guinea pigs: the repair phase after injury by cigarette smoke. Am Rev Respir Dis 123: 320–326.PubMedGoogle Scholar
  189. 189.
    McDonald DM (1987) Neurogenic inflammation in the respiratory tract: actions of sensory nerve mediators on blood vessels and epithelium of the airway mucosa. Am Rev Respir Dis 136: S65 — S71.PubMedGoogle Scholar
  190. 190.
    McDonald DM (1988) Neurogenic inflammation in the rat trachea I. Changes in venules, leucocytes and epithelial cells. J Neurocytol 17: 583–603.PubMedCrossRefGoogle Scholar
  191. 191.
    Richardson JB, Ferguson CC (1979) Neuromuscular structure and function in the airways. Fed Proc 38: 202–208.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Peter K. Jeffery
  • Mariusz J. Gizycki
  • Andrew V. Rogers

There are no affiliations available

Personalised recommendations