Hyaluronidase augments pneumolysin-mediated injury to human ciliated epithelium

Int J Infect Dis. 2007 Jan;11(1):11-5. doi: 10.1016/j.ijid.2005.09.002. Epub 2006 Feb 17.


Objectives: The main objective of this study was to investigate the effects of pneumococcal hyaluronidase (0.1-10microg/ml), alone and in combination with pneumolysin (50 and 100ng/ml), on human ciliated epithelium.

Methods: Ciliary beat frequency (CBF) and structural integrity of human ciliated respiratory epithelium in vitro were studied using a phototransistor technique and a visual scoring index, respectively.

Results: Hyaluronidase per se did not affect either CBF or the structural integrity of the epithelium. However, preincubation of the epithelial strips with hyaluronidase (10microg/ml) for 30min at 37 degrees C significantly potentiated pneumolysin-mediated ciliary slowing and epithelial damage. Hyaluronan, a substrate of hyaluronidase, had no effects on the ciliated respiratory epithelium in concentrations up to 100microg/ml and did not antagonize the injurious effects of pneumolysin on the epithelium. However, preincubation of the epithelial strips with hyaluronan (100microg/ml) was associated with attenuation of the ciliary slowing and epithelial damage induced by incubation of the strips with hyaluronidase (10microg/ml) for 30min at 37 degrees C followed by addition of pneumolysin (50ng/ml).

Conclusions: Although having no direct effects alone, hyaluronidase may contribute to pneumolysin-mediated damage and dysfunction to respiratory epithelium, thereby favoring colonization and subsequently extra-pulmonary dissemination of the pneumococcus.

MeSH terms

  • Bacterial Proteins / pharmacology
  • Calcium / blood
  • Calcium / metabolism
  • Cilia / drug effects*
  • Cilia / physiology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Epithelium / drug effects
  • Epithelium / physiology
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Humans
  • Hyaluronoglucosaminidase / chemistry
  • Hyaluronoglucosaminidase / pharmacology*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Streptolysins / pharmacology*


  • Bacterial Proteins
  • Streptolysins
  • plY protein, Streptococcus pneumoniae
  • Hyaluronoglucosaminidase
  • Calcium