Hyaluronidase augments pneumolysin-mediated injury to human ciliated epithelium.
OBJECTIVE
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.
Division of Pulmonology, Department of Medicine, Johannesburg Hospital and University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa. feldmanc@medicine.wits.ac.za
C
C
Feldman
R
R
Cockeran
M J
MJ
Jedrzejas
T J
TJ
Mitchell
R
R
Anderson
D001426:Bacterial Proteins / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002923:Cilia / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000737:chemistry / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D013301:Streptolysins / Q000494:pharmacology*
D001426:Bacterial Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D006821:Hyaluronoglucosaminidase; D002118:Calcium