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. 1995 Apr;63(4):1305–1310. doi: 10.1128/iai.63.4.1305-1310.1995

Breakdown of the round window membrane permeability barrier evoked by streptolysin O: possible etiologic role in development of sensorineural hearing loss in acute otitis media.

F Engel 1, R Blatz 1, J Kellner 1, M Palmer 1, U Weller 1, S Bhadki 1
PMCID: PMC173151  PMID: 7890388

Abstract

Sensorineural hearing loss is a common sequela of acute and chronic otitis media, and the round window membrane (RWM) is currently being considered as a major route for noxious agents to pass from the middle ear cavity to the cochlea. Streptococcus pneumoniae, a major causative agent of otitis media, and Streptococcus pyogenes A produce molecularly related toxins, pneumolysin and streptolysin O (SLO), that form large pores in target membranes. In this study, we analyzed the effects of SLO on the permeability of the RWM. Resected RWMs from a total of 104 guinea pigs were embedded between two chambers of an in vitro system. One chamber was designated as the tympanal (cis) compartment, and the other was designated as the inner ear (trans) compartment. The permeability of normal and SLO-damaged RWMs towards Na+, [14C]mannitol, and proteins was investigated. SLO evoked permeability defects dose dependently in the RWM with fluxes of both Na+ and [14C]mannitol being demonstrable over a time span of up to 8 h. Serum proteins and radioiodinated SLO were also shown to pass through the damage RWM. Scanning electron microscopy revealed the morphological correlates to these results. We propose that damage to the RWM by potent pore-forming cytolysins leads to leakage of ions from the perilymph. Ionic disequilibrium and passage of noxious macromolecules to the cochlea could contribute to disturbances of the inner ear function.

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Selected References

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  1. Arslan M. Modifications of the osmotic pressure of perilymph and endolymph. An hypothesis on the pathogenesis of Menière's disease. Acta Otolaryngol. 1969 Feb-Mar;67(2):360–377. doi: 10.3109/00016486909125463. [DOI] [PubMed] [Google Scholar]
  2. Asarch R., Abramson M., Litton W. B. Surgical anatomy of the guinea pig ear. Ann Otol Rhinol Laryngol. 1975 Mar-Apr;84(2 Pt 1):250–255. doi: 10.1177/000348947508400220. [DOI] [PubMed] [Google Scholar]
  3. Bernstein J. M. Recent advances in otitis media with effusion. Ann Allergy. 1985 Oct;55(4):544–551. [PubMed] [Google Scholar]
  4. Bhakdi S., Roth M., Sziegoleit A., Tranum-Jensen J. Isolation and identification of two hemolytic forms of streptolysin-O. Infect Immun. 1984 Nov;46(2):394–400. doi: 10.1128/iai.46.2.394-400.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bhakdi S., Tranum-Jensen J. Damage to cell membranes by pore-forming bacterial cytolysins. Prog Allergy. 1988;40:1–43. [PubMed] [Google Scholar]
  6. Bhakdi S., Tranum-Jensen J. Damage to mammalian cells by proteins that form transmembrane pores. Rev Physiol Biochem Pharmacol. 1987;107:147–223. doi: 10.1007/BFb0027646. [DOI] [PubMed] [Google Scholar]
  7. Bhakdi S., Tranum-Jensen J., Sziegoleit A. Mechanism of membrane damage by streptolysin-O. Infect Immun. 1985 Jan;47(1):52–60. doi: 10.1128/iai.47.1.52-60.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bhakdi S., Weller U., Walev I., Martin E., Jonas D., Palmer M. A guide to the use of pore-forming toxins for controlled permeabilization of cell membranes. Med Microbiol Immunol. 1993 Sep;182(4):167–175. doi: 10.1007/BF00219946. [DOI] [PubMed] [Google Scholar]
  9. Brady D. R., Pearce J. P., Juhn S. K. Permeability of round window membrane to 22Na or RISA. Arch Otorhinolaryngol. 1976 Nov 15;214(2):183–184. doi: 10.1007/BF00453616. [DOI] [PubMed] [Google Scholar]
  10. Buckingham L., Duncan J. L. Approximate dimensions of membrane lesions produced by streptolysin S and streptolysin O. Biochim Biophys Acta. 1983 Mar 23;729(1):115–122. doi: 10.1016/0005-2736(83)90462-5. [DOI] [PubMed] [Google Scholar]
  11. Comis S. D., Osborne M. P., Stephen J., Tarlow M. J., Hayward T. L., Mitchell T. J., Andrew P. W., Boulnois G. J. Cytotoxic effects on hair cells of guinea pig cochlea produced by pneumolysin, the thiol activated toxin of Streptococcus pneumoniae. Acta Otolaryngol. 1993 Mar;113(2):152–159. doi: 10.3109/00016489309135784. [DOI] [PubMed] [Google Scholar]
  12. English G. M., Northern J. L., Fria T. J. Chronic otitis media as a cause of sensorineural hearing loss. Arch Otolaryngol. 1973 Jul;98(1):18–22. doi: 10.1001/archotol.1973.00780020022006. [DOI] [PubMed] [Google Scholar]
  13. Goldberg B., Goycoolea M. V., Schleivert P. M., Shea D., Schachern P., Paparella M. M., Carpenter A. M. Passage of albumin from the middle ear to the inner ear in otitis media in the chinchilla. Am J Otolaryngol. 1981 Aug;2(3):210–214. doi: 10.1016/s0196-0709(81)80017-8. [DOI] [PubMed] [Google Scholar]
  14. Goycoolea M. V., Paparella M. M., Goldberg B., Schlievert P. M., Carpenter A. M. Permeability of the middle ear to staphylococcal pyrogenic exotoxin in otitis media. Int J Pediatr Otorhinolaryngol. 1980 Feb;1(4):301–308. doi: 10.1016/0165-5876(80)90004-x. [DOI] [PubMed] [Google Scholar]
  15. Goycoolea M. V., Paparella M. M., Juhn S. K., Carpenter A. M. Oval and round window changes in otitis media. Potential pathways between middle and inner ear. Laryngoscope. 1980 Aug;90(8 Pt 1):1387–1391. [PubMed] [Google Scholar]
  16. Gregg J. B., Roberts K. M., Colleran M. J. Ear disease and hearing loss, Pierre, South Dakota, 1962-1982. S D J Med. 1983 Oct;36(10):9–17. [PubMed] [Google Scholar]
  17. Hamaguchi Y., Morizono T., Juhn S. K. Round window membrane permeability to human serum albumin in antigen-induced otitis media. Am J Otolaryngol. 1988 Jan-Feb;9(1):34–40. doi: 10.1016/s0196-0709(88)80006-1. [DOI] [PubMed] [Google Scholar]
  18. Ikeda K., Morizono T. Changes of the permeability of round window membrane in otitis media. Arch Otolaryngol Head Neck Surg. 1988 Aug;114(8):895–897. doi: 10.1001/archotol.1988.01860200079023. [DOI] [PubMed] [Google Scholar]
  19. Ikeda K., Sakagami M., Morizono T., Juhn S. K. Permeability of the round window membrane to middle-sized molecules in purulent otitis media. Arch Otolaryngol Head Neck Surg. 1990 Jan;116(1):57–60. doi: 10.1001/archotol.1990.01870010061018. [DOI] [PubMed] [Google Scholar]
  20. Kawauchi H., DeMaria T. F., Lim D. J. Endotoxin permeability through the round window. Acta Otolaryngol Suppl. 1989;457:100–115. doi: 10.3109/00016488809138892. [DOI] [PubMed] [Google Scholar]
  21. Klein J. O. Otitis media and the development of speech and language. Pediatr Infect Dis. 1984 Jul-Aug;3(4):389–391. doi: 10.1097/00006454-198407000-00049. [DOI] [PubMed] [Google Scholar]
  22. Lee S. H., Woo H. W., Jung T. T., Lee C., Miller S. K., Park Y. M., Hwang S. K. Permeability of arachidonic acid metabolites through the round window membrane in chinchillas. Acta Otolaryngol Suppl. 1992;493:165–169. [PubMed] [Google Scholar]
  23. Lundman L. A., Holmquist L., Bagger-Sjöbäck D. Round window membrane permeability. An in vitro model. Acta Otolaryngol. 1987 Nov-Dec;104(5-6):472–480. doi: 10.3109/00016488709128277. [DOI] [PubMed] [Google Scholar]
  24. Lundman L., Bagger-Sjöbäck D., Juhn S. K., Morizono T. Pseudomonas aeruginosa exotoxin A and Haemophilus influenzae type b endotoxin. Effect on the inner ear and passage through the round window membrane of the chinchilla. Acta Otolaryngol Suppl. 1992;493:69–76. [PubMed] [Google Scholar]
  25. Lundman L., Juhn S. K., Bagger-Sjöbäck D., Svanborg C. Permeability of the normal round window membrane to Haemophilus influenzae type b endotoxin. Acta Otolaryngol. 1992;112(3):524–529. doi: 10.3109/00016489209137435. [DOI] [PubMed] [Google Scholar]
  26. Moore D. C., Best G. F. A sensorineural component in chronic otitis media. Laryngoscope. 1980 Aug;90(8 Pt 1):1360–1366. [PubMed] [Google Scholar]
  27. Morizono T., Giebink G. S., Paparella M. M., Sikora M. A., Shea D. Sensorineural hearing loss in experimental purulent otitis media due to Streptococcus pneumoniae. Arch Otolaryngol. 1985 Dec;111(12):794–798. doi: 10.1001/archotol.1985.00800140038006. [DOI] [PubMed] [Google Scholar]
  28. Paparella M. M., Brady D. R., Hoel R. Sensori-neural hearing loss in chronic otitis media and mastoiditis. Trans Am Acad Ophthalmol Otolaryngol. 1970 Jan-Feb;74(1):108–115. [PubMed] [Google Scholar]
  29. Paparella M. M., Goycoolea M. V., Schachern P. A., Sajjadi H. Current clinical and pathological features of round window diseases. Laryngoscope. 1987 Oct;97(10):1151–1160. doi: 10.1288/00005537-198710000-00006. [DOI] [PubMed] [Google Scholar]
  30. Paparella M. M., Kim C. S., Goycoolea M. V., Giebink S. Pathogenesis of otitis media. Ann Otol Rhinol Laryngol. 1977 Jul-Aug;86(4 Pt 1):481–492. doi: 10.1177/000348947708600407. [DOI] [PubMed] [Google Scholar]
  31. Paparella M. M., Morizono T., Le C. T., Mancini F., Sipilä P., Choo Y. B., Lidén G., Kim C. S. Sensorineural hearing loss in otitis media. Ann Otol Rhinol Laryngol. 1984 Nov-Dec;93(6 Pt 1):623–629. doi: 10.1177/000348948409300616. [DOI] [PubMed] [Google Scholar]
  32. Paparella M. M., Oda M., Hiraide F., Brady D. Pathology of sensorineural hearing loss in otitis media. Ann Otol Rhinol Laryngol. 1972 Oct;81(5):632–647. doi: 10.1177/000348947208100503. [DOI] [PubMed] [Google Scholar]
  33. Paparella M. M. Review of sensorineural hearing loss. Am J Otol. 1984 Apr;5(4):311–314. [PubMed] [Google Scholar]
  34. Sando I., Masuda Y., Wood R. P., 2nd, Hemenway W. G. Perilymphatic communication routes in guinea pig cochlea. Ann Otol Rhinol Laryngol. 1971 Dec;80(6):826–834. doi: 10.1177/000348947108000609. [DOI] [PubMed] [Google Scholar]
  35. Schachern P. A., Paparella M. M., Goycoolea M. V., Duvall A. J., 3rd, Choo Y. B. The permeability of the round window membrane during otitis media. Arch Otolaryngol Head Neck Surg. 1987 Jun;113(6):625–629. doi: 10.1001/archotol.1987.01860060051014. [DOI] [PubMed] [Google Scholar]
  36. Schachern P. A., Paparella M. M., Goycoolea M., Goldberg B., Schlievert P. The round window membrane following application of staphylococcal exotoxin: an electron microscopic study. Laryngoscope. 1981 Dec;91(12):2007–2017. doi: 10.1288/00005537-198112000-00003. [DOI] [PubMed] [Google Scholar]
  37. Walker J. A., Allen R. L., Falmagne P., Johnson M. K., Boulnois G. J. Molecular cloning, characterization, and complete nucleotide sequence of the gene for pneumolysin, the sulfhydryl-activated toxin of Streptococcus pneumoniae. Infect Immun. 1987 May;55(5):1184–1189. doi: 10.1128/iai.55.5.1184-1189.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

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