Lung Defenses

  • J. Linder
  • J. H. Sisson


The lung is unique among the visceral organs because it is exposed to the external environment. Remarkably, there is continuity between the tip of the nostril and the most distal alveoli. Thousands of cubic feet of air pass through the airways each day, air that contains noxious gases, dusts, particulate material, and microbial organisms that alone or in combination can damage the lung. Fortunately, the lung has multiple defense mechanisms that protect against potentially injurious agents.


Alveolar Macrophage Adult Respiratory Distress Syndrome Mucociliary Clearance Lung Defense Situs Inversus 
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.
    Verhoef J. Host-pathogen relationships in respiratory tract infections. Clin Ther 1991; 13 (1): 172–180.PubMedGoogle Scholar
  2. 2.
    Coonrod JD, Rehm SR, Yoneda K. Pneumococcal killing in the alveolus. Evidence for a nonphagocytic defense mechanism for early clearance. Chest 1983; 83 (Suppl.): 895–905.Google Scholar
  3. 3.
    Jonsson S, Musher DM, Goree A, Lawrence EC. Human alveolar lining material and antibacterial defenses. Am Rev Respir Dis 1986; 133 (1): 136–140.PubMedGoogle Scholar
  4. 4.
    Reynolds HY. Lung inflammation: Role of endogenous chemotactic factors in attracting polymorphonuclear granulocytes. Am Rev Respir Dis 1983; 127 (2): S16–S25.PubMedGoogle Scholar
  5. 5.
    Sibille Y, Reynolds HY. Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Respir Dis 1990; 141 (2): 471–501.PubMedCrossRefGoogle Scholar
  6. 6.
    Fisher ES, Lauffenburger DA, Daniele RP. The effect of alveolar macrophage Chemotaxis on bacterial clearance from the lung surface. Am Rev Respir Dis 1988; 137 (5): 1129–1134.PubMedCrossRefGoogle Scholar
  7. 7.
    Valberg PA, Jensen WA, Rose RM. Cell organelle motions in bronchoalveolar lavage macrophages from smokers and nonsmokers. Am Rev Respir Dis 1990; 141: 1272–1279.PubMedCrossRefGoogle Scholar
  8. 8.
    Waldorf AR, Levitz SM, Diamond RD. In vivo bronchoalveolar macrophage defense against Rhizopus oryzae and Aspergillus fumigatus. J Infect Dis 1984; 150 (5): 752–760.CrossRefGoogle Scholar
  9. 9.
    Elstad MR. Aspergillosis and lung defenses. Semin Respir Infect 1991; 6 (1): 27–36.PubMedGoogle Scholar
  10. 10.
    Flesch IE, Schwamberger G, Kaufmann SH. Fungicidal activity of IFN-gamma-activated macrophages. Extracellular killing of Cryptococcus neoformans. J Immunol 1989; 142 (9): 3219–3224.PubMedGoogle Scholar
  11. 11.
    Tuomanen E, Rich R, Zak O. Induction of pulmonary inflammation by components of the pneumococcal cell surface. Am Rev Respir Dis 1987; 135 (4): 869–874.PubMedGoogle Scholar
  12. 12.
    Harris SE, Nelson S, Astry CL, Bainton BG, Summer WR. Endotoxin-induced suppression of pulmonary antibacterial defenses against Staphylococcus aureus. Am Rev Respir Dis 1988; 138 (6): 1439–1443.PubMedCrossRefGoogle Scholar
  13. 13.
    Levi MH, Pasculle AW, Dowling JN. Role of the alveolar macrophage in host defense and immunity to Legionella micdadei pneumonia in the guinea pig. Microb Pathog 1987; 2 (4): 269–282.PubMedCrossRefGoogle Scholar
  14. 14.
    Debs RJ, Fuchs HJ, Philip R, et al. Lung-specific delivery of cytokines induces sustained pulmonary and systemic immunomodulation in rats. J Immunol 1988; 140 (10): 3482–3488.PubMedGoogle Scholar
  15. 15.
    Rhodin AJ. The ciliated cell. Ultrastructure and function of the human tracheal mucosa. Amer Ref Resp Dis 1966; 93: 1–15.Google Scholar
  16. 16.
    Dalhamn T. Mucus flow and ciliary activity in the trachea of healthy rats and rats exposed to respiratory irritant gases. Acta Physiol Scand (Suppl. 123) 1956; 36: 1–163.CrossRefGoogle Scholar
  17. 17.
    Iravani J, Van As A. Mucus transport in the tracheobronchial tree of normal and bronchitic rats. J Pathol 1972; 106: 81–93.PubMedCrossRefGoogle Scholar
  18. 18.
    Sleigh MA. The nature and action of respiratory tract cilia. In: Brain J, Proctor D, Reid L, ed. Respiratory defense mechanisms. New York: Dekker, 1977: 247–289.Google Scholar
  19. 19.
    Fick RB, Jr. Cell-mediated antibacterial defenses of the distal airways. Am Rev Respir Dis 1985; 131 (5): 543–548.Google Scholar
  20. 20.
    Lipscomb MF. Lung defenses against opportunistic infections. Chest 1989; 96 (6): 1393–1399.PubMedCrossRefGoogle Scholar
  21. 21.
    Dannenberg AJ. Delayed-type hypersensitivity and cell-mediated immunity in the pathogenesis of tuberculosis. Immunol Today 1991; 12 (7): 228–233.PubMedCrossRefGoogle Scholar
  22. 22.
    Gryzan S, Paradis IL, Zeevi A, et al. Unexpectedly high incidence of Pneumocystis carinii infection after lung-heart transplantation. Implications for lung defense and allograft survival. Am Rev Respir Dis 1988; 137 (6): 1268–1274.PubMedCrossRefGoogle Scholar
  23. 23.
    Hoffman RM, Dauber JH, Paradis IL, Griffith BP, Hard-esty RL. Alveolar macrophage migration after lung transplantation. Am Rev Respir Dis 1991; 143: 834–838.PubMedCrossRefGoogle Scholar
  24. 24.
    Iwata M, Sato A. Morphological and immunohistochem-ical studies of the lungs and bronchus-associated lymphoid tissue in a rat model of chronic pulmonary infection with Pseudomonas aeruginosa. Infect Immun 199 l;p59(4): 1514–1520.Google Scholar
  25. 25.
    Toews GB, Hansen EJ, Strieter RM. Pulmonary host defenses and oropharyngeal pathogens. Am J Med 1990; 88 (5A): 205–245.CrossRefGoogle Scholar
  26. 26.
    Shennib H, Mulder DS, Chiu RC. The effects of pulmonary atelectasis and reexpansion on lung cellular immune defenses. Arch Surg 1984; 119 (3): 274–277.PubMedCrossRefGoogle Scholar
  27. 27.
    Marshall BC, Carroll KC. Interaction between Pseudomonas aeruginosa and host defenses in cystic fibrosis. Semin Respir Infect 1991; 6 (1): 11–18.PubMedGoogle Scholar
  28. 28.
    Siewert A. Uber einen fall von bronchiectasie bei einem patienten mit situs inversus viscerum. Berl Klin Wochen-schr 1904; 41: 139–141.Google Scholar
  29. 29.
    Kartagener M. Zur Pathogenese der bronchiektasien. I. Mitteilung: Bronchiektasien bei situs viscerum inversus. Beitr Klin Tuberk 1933, 83: 498–501.Google Scholar
  30. 30.
    Afzelius BA. A human syndrome caused by immotile cilia. Science 1976; 193: 317–319.PubMedCrossRefGoogle Scholar
  31. 31.
    Afzelius BA, Eliasson R. Flagellar mutants in man: On the heterogeneity of the immotile-cilia syndrome. J Ultra-struct Res 1979; 69: 43–52.CrossRefGoogle Scholar
  32. 32.
    Afzelius BA. The immotile cilia syndrome and other ciliary diseases. Int Rev Exp Pathol 1979; 19: 1–43.PubMedGoogle Scholar
  33. 33.
    Sturgess J, Thompson M, Czegledy-Nagy E, Turner J. Genetic aspects of immotile cilia syndrome. Am J Med Genet 1986; 25: 149–160.PubMedCrossRefGoogle Scholar
  34. 34.
    Afzelius BA. Disorders of ciliary motility. Hosp Pract 1986; 21 (3): 73–80.Google Scholar
  35. 35.
    Pavia D, Agnew JE, Bateman JRM, et al. Lung mucociliary clearance in patients with Young’s syndrome. Chest 1981; 80: 892–893.PubMedCrossRefGoogle Scholar
  36. 36.
    Waite DA, Wakefield SJ, MackayJB, Ross IT. Mucociliary transport and ultrastructural abnormalities in Polynesian bronchiectasis. Chest 1981; 80 (Suppl): 896–898.PubMedCrossRefGoogle Scholar
  37. 37.
    Douglas SD, Musson RA. Phagocytic defects—monocytes/ macrophages. Clin Immunol Immunopathol 1986; 40(l):62–68.Google Scholar
  38. 38.
    Quie PG. Lung defense against infection. J Pediatr 1986; 108: 813–816.PubMedCrossRefGoogle Scholar
  39. 39.
    White JC, Nelson S, Winkelstein JA, Booth FV, Jakab GJ. Impairment of antibacterial defense mechanisms of the lung by extrapulmonary infection. J Infect Dis 1986; 153 (2): 202–208.PubMedCrossRefGoogle Scholar
  40. 40.
    Nelson S, Chidiac C, Bagby G, Summer WR. Endotoxin-induced suppression of lung host defenses. J Med (West-bury) 1990; 21 (1–2): 85–103.Google Scholar
  41. 41.
    Ozaki T, Maeda M, Hayashi H, et al. Role of alveolar macrophages in the neutrophil-dependent defense system against Pseudomonas aeruginosa infection in the lower respiratory tract. Amplifying effect of muramyl dipeptide analog. Am Rev Respir Dis 1989; 140 (6): 1595–1601.PubMedCrossRefGoogle Scholar
  42. 42.
    Pennington JE, Rössing TH, Boerth LW, Lee TH. Isolation and partial characterization of a human alveolar macrophage-derived neutrophil-activating factor. J Clin Invest 1985; 75 (4): 1230–1237.PubMedCrossRefGoogle Scholar
  43. 43.
    Ehouman A, Pinchon MC, Escudier E, Bernaudin JF. Ultrastructural abnormalities of respiratory cilia. Vir-chows Arch B Cell Pathol 1985; 48: 87–95.CrossRefGoogle Scholar
  44. 44.
    Rosenow EC, III, Wilson WR, Cockerill FR, III. Pulmonary disease in the immunocompromised host. 1. Mayo Clin Proc 1985*;60(7):473–487.Google Scholar
  45. 45.
    Martin TR, Altman LC, Alvares OF. The effects of severe protein-calorie malnutrition on antibacterial defense mechanisms in the rat lung. Am Rev Respir Dis 1983; 128 (6): 1013–1019.PubMedGoogle Scholar
  46. 46.
    Shellito J, Suzara VV, Blumenfeld W, Beck JM, Steger HJ, Ermak TH. A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. J Clin Invest 1990; 85 (5): 1686–1693.PubMedCrossRefGoogle Scholar
  47. 47.
    Robinson A, Abraham E. Hemorrhage in mice produces alterations in pulmonary B cell repertoires. J Immunol 1990; 145 (11): 3734–3739.PubMedGoogle Scholar
  48. 48.
    Musher DM, Watson DA, Nickeson D, Gyorkey F, Lahart C, Rossen RD. The effect of HIV infection on phagocytosis and killing of Staphylococcus aureus by human pulmonary alveolar macrophages. Am J Med Sei 1990; 299 (3): 158–163.CrossRefGoogle Scholar
  49. 49.
    Wallaert B, Aerts C, Bart F, et al. Alveolar macrophage dysfunction in systemic lupus erythematosus. Am Rev Respir Dis 1987; 136 (2): 293–297.PubMedCrossRefGoogle Scholar
  50. 50.
    Weissler JC, Nicod LP, Toews GB. Pulmonary natural killer cell activity is reduced in patients with bronchogenic carcinoma. Am Rev Respir Dis 1987; 135 (6): 1353–1357.PubMedGoogle Scholar
  51. 51.
    Callery MP, Kamei T, Mangino MJ, Flye MW. Organ interactions in sepsis. Host defense and the hepatic-pulmonary macrophage axis. Arch Surg 1991; 126(1):28— 32.Google Scholar
  52. 52.
    Waldorf AR, Ruderman N, Diamond RD. Specific susceptibility to mucormycosis in murine diabetes and bron-choalveolar macrophage defense against Rhizopus. J Clin Invest 1984; 74 (1): 150–160.PubMedCrossRefGoogle Scholar
  53. 53.
    Hostetter MK. Handicaps to host defense. Effects of hyperglycemia on C3 and Candida albicans. Diabetes 1990; 39 (3): 271–275.PubMedCrossRefGoogle Scholar
  54. 54.
    Sima AA, O’Neill SJ, Naimark D, Yagihashi S, Klass D. Bacterial phagocytosis and intracellular killing by alveolar macrophages in BB rats. Diabetes 1988; 37 (5): 544–549.PubMedCrossRefGoogle Scholar
  55. 55.
    Mellencamp MA, Preheim LC. Pneumococcal pneumonia in a rat model of cirrhosis: Effects of cirrhosis on pulmonary defense mechanisms against Streptococcus pneumoniae. Infect Dis 1991; 163 (1): 102–108.CrossRefGoogle Scholar
  56. 56.
    Martin TR, Pistorese BP, Hudson LD, Maunder RJ. The function of lung and blood neutrophils in patients with the adult respiratory distress syndrome. Implications for the pathogenesis of lung infections. Am Rev Respir Dis 1991; 144 (2): 254–262.PubMedCrossRefGoogle Scholar
  57. 57.
    Binkhorst GJ, Henricks PA, VD Inghts, Hajer R, Nijkamp FP. The effect of stress on host defense system and on lung damage in calves experimentally infected with Pasteurella haemolytica type Al. Zentralbl Veterinaemed Reihe A 1990; 37 (7): 525–536.CrossRefGoogle Scholar
  58. 58.
    Sisson JH, Tuma DJ, Rennard SI. Acetaldehyde-medi-ated cilia dysfunction in bovine bronchial epithelial cells. Am J Physiol 1991; 260: L29–L36.PubMedGoogle Scholar
  59. 59.
    Gilmour MI, Hmieleski RR, Stafford EA, Jakab GJ. Suppression and recovery of the alveolar macrophage phagocytic system during continuous exposure to 0.5 ppm ozone. Exp Lung Res 1991; 17 (3): 547–588.PubMedCrossRefGoogle Scholar
  60. 60.
    Nelson S, Summer WR, Jakab GJ. Aminophylline-in-duced suppression of pulmonary antibacterial defenses. Am Rev Respir Dis 1985; 131 (6): 923–927.PubMedGoogle Scholar
  61. 61.
    Nelson S, Summer WR, Terry PB, Warr GA, Jakab GJ. Erythromycin-induced suppression of pulmonary antibacterial defenses. A potential mechanism of superinfection in the lung. Am Rev Respir Dis 1987; 136 (5): 1207–1212.PubMedCrossRefGoogle Scholar
  62. 62.
    Shayevitz JR, Varani J, Ward PA, Knight PR. Halothane and isoflurane increase pulmonary artery endothelial cell sensitivity to oxidant-mediated injury. Anesthesiology 1991; 74 (6): 1067–1077.PubMedCrossRefGoogle Scholar
  63. 63.
    Reynolds HY. Lung Inflammation: Normal host defense or a complication of some diseases? Annu Rev Med 1987; 38 (l): 295–323.PubMedCrossRefGoogle Scholar
  64. 64.
    Sherman MP, Evans MJ, Campbell LA. Prevention of pulmonary alveolar macrophage proliferation in newborn rabbits by hyperoxia. J Pediatr 1988; 112 (5): 782–786.PubMedCrossRefGoogle Scholar
  65. 65.
    Hubbard RC, McElvaney NG, Sellers SE, Healy JT, Czer-ski DB, Crystal RG. Recombinant DNA-produced alpha 1-antitrypsin administered by aerosol augments lower respiratory tract antineutrophil elastase defenses in individuals with alpha-1-antitrypsin deficiency. J Clin Invest 1989; 84 (4): 1349–1354.PubMedCrossRefGoogle Scholar
  66. 66.
    Sanderson M, Dirksen E. Mechanosensitive and beta-adrenergic control of the ciliary beat frequency of mammalian respiratory tract cells in culture. Am Rev Respir Dis 1989; 139: 432–440.PubMedCrossRefGoogle Scholar
  67. 67.
    Yeates D, Spektor D, Pitt B. Effect of orally administered orciprenaline on tracheobronchial mucociliary clearance. Eur J Respir Dis 1986; 69: 100–108.PubMedGoogle Scholar
  68. 68.
    Foster WM, Langenback E, Bohning DE, Bergofsky EH. Quantitation of mucus clearance in peripheral lung and comparison with tracheal and bronchial mucus transport velocities in man: Adrenergics return depressed clearance and transport velocities in asthmatics to normal. Am Rev Respir Dis 1978;l77(Suppl.):337 (abstr.).Google Scholar
  69. 69.
    Wanner A, Maurer D. Abraham W, Szepfalusi Z, Sielczak M. Effects of chemical mediators of anaphylaxis on ciliary function. J Allergy Clin Immunol 1983; 72: 663–667.PubMedCrossRefGoogle Scholar
  70. 70.
    Mussatto D, Lourenco R. The effect of inhaled histamine on human tracheal mucus velocity and bronchial mucociliary clearance. Am Rev Respir Dis 1988; 138: 775–779.PubMedCrossRefGoogle Scholar
  71. 71.
    Bisgaard H, Pedersen M. SRS-A leukotrienes decreases the activity of human respiratory cilia. Clin Allergy 1987; 17: 95–103.PubMedCrossRefGoogle Scholar
  72. 72.
    Tamaoki J, Kobayaski K, Sakai N, Chiyotani A, Kane-mura T, Takizawa T. Effect of bradykinin on airway ciliary motility and its modulation by neutral endopepti-dase. Am Rev Respir Dis 1989; 140: 430–435.PubMedCrossRefGoogle Scholar
  73. 73.
    Lindberg S, Mercke U. Bradykinin accelerates mucociliary activity in rabbit maxillary sinus. Acta Otolaryngol (Stockh) 1988; 101: 114–121.CrossRefGoogle Scholar
  74. 74.
    Wong L, Miller I, Yeates D. Regulatory pathways for the stimulation of canine tracheal ciliary beat frequency by bradykinin. J Physiol (London) 1990; 422: 421–431.Google Scholar
  75. 75.
    Kondo M, Tamaoki J, Takizawa T. Neutral endopeptid-ase inhibitor potentiates the tachykinin-induced increase in ciliary beat frequency in rabbit trachea. Am Rev Respir Dis 1990; 142: 403–406.PubMedCrossRefGoogle Scholar
  76. 76.
    Kobayashi K, Tamaoki J, Sakai N, Kanemura T, Horii S, Takizawa T. Angiotensin II stimulates airway ciliary motility in rabbit cultured tracheal epithelium. Acta Physiol Scand 1990; 138: 497–502.PubMedCrossRefGoogle Scholar
  77. 77.
    Khan A, Bengtsson B, Lindberg S. Influence of substance P on ciliary beat frequency in airway isolated preparations. Eur J Pharmacol 1986; 130: 91–96.PubMedCrossRefGoogle Scholar
  78. 78.
    Lindberg S, Mercke U, Uddman R. The morphological basis for the effect of substance P on mucociliary activity in rabbit maxilliary sinus. Acta Otolaryngol (Stockh) 1986; 101: 314–319.CrossRefGoogle Scholar
  79. 79.
    Dadaina J, Yin S, Laurenzi G. Studies of mucus flow in the mammalian respiratory tract. Am Rev Respir Dis 1971; 103: 808–815.Google Scholar
  80. 80.
    Verdugo P. Calcium-dependent hormonal stimulation of ciliary activity. Nature (London) 1980; 283: 764–765.CrossRefGoogle Scholar
  81. 81.
    Wanner A, Sielczak M, Mella J, Abraham W. Ciliary responsiveness in allergic and nonallergic airways. J Appl Physiol 1986; 60: 1967–1971.PubMedGoogle Scholar
  82. 82.
    Villalon M, Hinds T, Verdugo P. Stimulus-response coupling in mammalian ciliated cells. Demonstration of two mechanisms of control for cytosolic [Ca2+]. Biophys J 1989; 56: 1255–1258.PubMedCrossRefGoogle Scholar
  83. 83.
    Jonsson MS, McCormick JR, Gillies CG, Gondos B. Kart-agener’s syndrome with motile spermatozoa. N Engl J Med 1982; 307: 1131–1133.PubMedCrossRefGoogle Scholar
  84. 84.
    Sturgess JM, ChaoJ, Wong J, Aspin N, Turner JAP. Cilia with defective radial spokes—A cause of human respiratory disease. N Engl J Med 1979; 300: 53–56.PubMedCrossRefGoogle Scholar
  85. 85.
    Sturgess J M, ChaoJ, Turner J A. Tranposition of ciliary microtubules. Another cause of impaired ciliary motility. N Engl J Med 1980; 303: 318–322.Google Scholar
  86. 86.
    Schneeberger EE, McCormack J, Issenberg HJ, Schuster SR, Gerald PS. Heterogeneity of ciliary morphology in the immotile-cilia syndrome in man. J Ultrastruct Res 1980; 73: 34–43.PubMedCrossRefGoogle Scholar
  87. 87.
    Afzelius BA, Camner P, Mossberg B. Acquired ciliary defects compared to those seen in the immotile-cilia syndrome. Eur J Respir Dis 1983; 64: 5–10.Google Scholar
  88. 88.
    Carson JL, Collier AM. Ciliary defects: Cell biology and clinical perspectives. Adv Pediatr 1988; 35: 139–165.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • J. Linder
  • J. H. Sisson

There are no affiliations available

Personalised recommendations