The concentration of major basic protein (MBP) of the eosinophilic granules in bronchial expectoration (Sputum) were measured by radioimmunoassay in 204 subjects suffering from various illnesses of both the respiratory tract and other systems. 31 of these subjects were later revealed to have asthma and all had very high sputum MBP levels. The MBP level was much greater in asthmatics than any other respiratory or non-respiratory ailment and in a statistically significant fashion (p less than 0.001). 25 other subjects who were in hospital for exacerbations of asthma were subsequently tested; their MBP concentrations were higher still. During the course of their hospital stay the sputum MBP levels fell significantly following treatment with steroids and broncho-dilators. The measurement of the MBP level would seem useful in those situations where the diagnosis of asthma is not evident from the history and may help in predicting the effectiveness of steroid treatment.
We tested the effects of four eosinophil granule cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), on guinea pig tracheal epithelium in vitro. Examination by inverted microscopy revealed that MBP, both the form stabilized by alkylation of sulfhydryl groups as well as the native form of the molecule, ECP, EPO by itself, as well as EPO + H2O2 + halide, but not EDN, cause dose-related damage to the tracheal epithelium. The lowest concentrations of MBP and ECP causing damage were 10 and 100 µg/ml, respectively. In contrast, EDN, although biochemically similar to ECP, did not damage the tracheal epithelium in concentrations of up to 200 µg/ml. MBP caused exfoliation, as well as bleb formation and ciliostasis. EPO in the presence of the H2O2-producing enzyme glucose oxidase (GO), Cl−, 0.11 M, and iodide caused ciliostasis, bleb formation, and exfoliation of epithelial cells at concentrations as low as 1 U/ml (3.9 µg/ml). EPO + GO in the presence of Cl− , 0.11 M, alone or with Cl− and I , 10−4 M, or Cl− and Br− , 5 × 10−5 M, were all toxic to epithelium. Surprisingly, EPO by itself caused partial ciliostasis, bleb formation, and exfoliation of epithelial cells in a dose-related manner at concentrations as low as 10 to 30 U/ml (39 to 121 (µg/ml). These results confirm prior observations showing the toxicity of MBP to tracheal epithelium and indicate that ECP and EPO alone, as well as EPO + GO + halide, cause damage. Thus, several eosinophil granule proteins are able to damage respiratory epithelium.
