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Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Role of the epithelium
N A Flavahan1, N R Slifman, G J Gleich
1Department of Physiology, Mayo Clinic, Rochester, MN 55905.
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.
Insights
Major basic protein (MBP) from eosinophils damages airway epithelium, increasing airway smooth muscle hyperreactivity. This finding may explain chronic respiratory disease symptoms.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Immunology
Background:
- Major basic protein (MBP) is an eosinophil granule protein.
- MBP is cytotoxic to respiratory epithelium and found in asthmatic airways.
Purpose of the Study:
- To investigate the effects of MBP on airway smooth muscle responsiveness.
- To determine if MBP contributes to airway hyperreactivity in respiratory diseases.
Main Methods:
- Guinea pig tracheal rings, with and without epithelium, were incubated with human MBP.
- Isometric tension recordings were used to measure airway smooth muscle reactivity to acetylcholine and histamine.
Main Results:
- MBP did not alter the reactivity of tracheal rings lacking epithelium.
- MBP significantly increased the reactivity of intact tracheal rings to acetylcholine and histamine.
Conclusions:
- MBP enhances airway smooth muscle hyperreactivity by impairing epithelial cell function.
- MBP's effect on airway epithelium may contribute to the hyperreactivity seen in chronic respiratory diseases.