Elevated levels of macrophage-stimulating protein in induced sputum of patients with bronchiectasis.
We recently showed that macrophage-stimulating protein (MSP), a serum protein homologous to hepatocyte growth factor, promotes ciliary motility by activating its receptor, RON, on the airway ciliated epithelium. To investigate the functional involvement of MSP and RON in bronchiectasis, in which mucociliary clearance (MCC) is impaired, first we examined RON expression on the bronchial ciliated epithelium of patients with bronchiectasis. We confirmed RON expression at the apical surface of bronchial ciliated epithelium of patients with bronchiectasis as well as those of normal human bronchus. Next, we examined whether MSP is present in sputum of patients with bronchiectasis 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 serum 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 biologically active form, (ii) MSP is increased in patients with bronchiectasis compared with normal controls. Taken together, our findings suggest that increased MSP may be involved in compensation for impaired MCC in bronchiectasis.
Takano
Y
Y
First Department of Internal Medicine, IMEG, Kumamoto University School of Medicine, Japan.
Sakamoto
O
O
Suga
M
M
Suda
T
T
Ando
M
M
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001987:Bronchiectasis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002925:Ciliary Motility Disorders / Q000209:etiology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006133:Growth Substances / Q000032:analysis*; D017228:Hepatocyte Growth Factor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013183:Sputum / Q000737:chemistry* / Q000166:cytology; D014797:Vital Capacity / Q000502:physiology
D006133:Growth Substances; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D020794:Receptor Protein-Tyrosine Kinases