Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Role of the epithelium

Abstract

Major basic protein (MBP), one of several cationic proteins associated with the eosinophil granule, is cytotoxic to respiratory epithelium and is present in the sputum of asthmatics and on damaged bronchial epithelium from patients dying of asthma. The present experiments were performed in order to determine the effects of MBP on the responsiveness of airway smooth muscle. Rings of guinea pig trachea, in some of which the epithelium had been gently removed by rubbing, were incubated for 5 h in modified Krebs-Ringer bicarbonate solution containing buffer or human MBP (100 micrograms/ml). The tracheal rings were then suspended for isometric tension recording in organ chambers filled with Krebs-Ringer solution containing indomethacin. MBP did not affect the reactivity of rings in which the epithelium had been removed, but significantly augmented that of unrubbed rings to acetylcholine and histamine. The results suggest that MBP, by inhibiting the function of epithelial but not smooth muscle cells, causes hyperreactivity of respiratory smooth muscle, which may contribute to the hyperreactivity observed in chronic respiratory disease.