Elevated levels of macrophage-stimulating protein in induced sputum of patients with bronchiectasis

We recently showed that macrophage-stimulating protein (MSP), a serum prote in homologous to hepatocyte growth factor, promotes ciliary motility by act ivating its receptor, RON, on the airway ciliated epithelium. To investigat e the functional involvement of MSP and RON in bronchiectasis, in which muc ociliary clearance (MCC) is impaired, first we examined RON expression on t he bronchial ciliated epithelium of patients with bronchiectasis. We confir med RON expression at the apical surface of bronchial ciliated epithelium o f patients with bronchiectasis as well as those of normal human bronchus. N ext, we examined whether MSP is present in sputum of patients with bronchie ctasis and normal control subjects. By Western blotting, we found that half of the MSP in sputum is present as a biologically active alpha/beta chain heterodimer (mature MSP). In addition, we found that the MSP concentrations in sputum were significantly elevated in patients with bronchiectasis (n = 8; 16.8+/-3.0 ng ml(-1)) compared with normal controls (n = 9; 8.4 +/- 2.4 ng ml(-1); P < 0.05). In contrast, the difference in concentrations of ser um MSP (pro-MSP) was not significant between the two groups. These results indicate that (i) MSP is supplied to the airways and converted to a biologi cally active form, (ii) MSP is increased in patients with bronchiectasis co mpared with normal controls. Taken together, our findings suggest that incr eased MSP may be involved in compensation for impaired MCC in bronchiectasi s.