The effect of purified human eosinophil major basic protein on mammalian ciliary activity

Eosinophil granulocyte infiltration in a variety of lung disorders may directly damage local tissue by release of granule contents. A principal constituent of eosinophil granules is the major basic protein (MBP). Previous light and electron microscopic observations have indicated that guinea pig and human MBP produce detachment of tracheal epithelial cells and cessation of ciliary activity. To quantitate the damage, selected regions of the epithelial surface of rabbit tracheal explants were videotaped before and after treatment with human MBP. Tapes were analyzed for ciliary beat frequency and the extent of zones along the epithelial surface displaying ciliary activity. The MBP at 0.1 mg/ml reduced beat frequency and significantly reduced the measured zones of ciliary activity. Also, MBP at 0.7 mg/ml significantly reduced beat frequency and the measured zone of ciliary activity on the epithelial surface. Beat frequency was lowered by 27% within 10 min, with only 1% further decrease by 60 min. The zones of ciliary activity on the epithelium were continuously decreased throughout the 60 min to 29% of the initially active zone. To examine whether MBP was capable of direct inhibition of ciliary activity, isolated porcine tracheal ciliary axonemes, the structural organelles of individual cilia, were treated with human MBP. Concentrations above 67 micrograms/ml of MBP were completely inhibitory to reactivated isolated axonemes, 67 micrograms/ml stopped activity within 10 min, and 27 micrograms/ml stopped activity within 15 min. Pretreatment of isolated axonemes with increasing concentrations of MBP resulted in decreasing ATPase activity. These effects were not attributable to pH alteration.(ABSTRACT TRUNCATED AT 250 WORDS)