Streptococcus pneumoniae-induced inhibition of rat ependymal cilia is attenuated by antipneumolysin antibody

Abstract

Ciliated ependymal cells line the ventricular surfaces and aqueducts of the brain. In ex vivo experiments, pneumolysin caused rapid inhibition of the ependymal ciliary beat frequency and caused ependymal cell disruption. Wild-type pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but penicillin lysis of wild-type, not pneumolysin-deficient, pneumococci increased the extent of ciliary inhibition. This effect was abolished by antipneumolysin antibody. Ependymal ciliary stasis by purified pneumolysin was also blocked by the addition of antipneumolysin monoclonal antibodies. These data show that antibiotic lysis of Streptococcus pneumoniae can be detrimental to the ciliated ependyma and that antipneumolysin antibody may have a therapeutic potential.

FIG. 1.

Inhibition of the ependymal CBF by intact wild-type pneumococci (A) or intact pneumolysin-negative pneumococci (B). Ependyma were given 10⁸ CFU/ml (▴), 10⁷ CFU/ml (□), or 10⁶ CFU/ml (•). Each point is the mean ± the standard error of the mean of results from between five and nine independent experiments.

FIG. 2.

Effects of penicillin-lysed wild-type (D39) pneumococci at 10⁸ CFU/ml (A) and at 10⁷ CFU/ml (B) on the ependymal CBF in the absence (□) and presence (•) of antipneumolysin antibody (PLY-4). (C) Effects of penicillin-lysed PLN-A at 10⁷ CFU/ml (✠) and 10⁸ CFU/ml (◊) and of D39 at 10⁶ CFU/ml (▾) on the ependymal CBF. Each point represents the mean ± the standard error of the mean of results from between five and seven independent experiments.

FIG. 3.

Effect of 1 HU of pneumolysin (•) on the cultured ependymal CBF compared to that of no pneumolysin (control) (□). The graph shows a significant (*, P < 0.05) inhibition compared with values for the control at 2, 24, and 72 h after exposure to pneumolysin followed by a recovery in the CBF to control levels. Each point is the mean ± the standard error of the mean of results from four independent experiments.