Cigarette smoking has diverse effects on the structure and function of the lung. Smoking appears to reduce the levels of Clara cell 10 kDa protein (CC10) in the alveolar lining fluid, but the influence of smoking serum on CC10 levels is still debated, and it has not been clear whether smoking reduces the number of CC10-producing lung cells. The aims of this study were to clarify the influence of smoking on CC10 levels in the alveolar lining fluid and bloodstream, and on the number of CC10-producing lung cells.CC10 concentrations were measured in sera and bronchoalveolar lavage (BAL) fluids, by means of enzyme-linked immunosorbent assay using monoclonal and polyclonal antibody, and the immunohistochemical expression of CC10 was examined in the lungs of nonsmokers and smokers using the monoclonal antibody, TY-5, against CC10/human urinary protein-1. CC10 concentrations in sera and in BAL fluids from healthy smokers were significantly lower than in healthy nonsmokers. Immunohistochemical expression of CC10 was found exclusively in nonciliated bronchiolar epithelial cells. As compared to that of nonsmokers, the mean percentage of CC10-positive bronchiolar epithelial cells was significantly decreased in lung tissue specimens obtained from smokers who had normal results in pulmonary function tests.It was concluded that smoking reduces the proportion of Clara cell 10 kDa protein-producing bronchiolar epithelial cells, resulting in decreased levels of Clara cell 10 kDa protein in the lower respiratory tract and in the bloodstream. The protein is a new blood biochemical and immunohistochemical marker, reflecting structural changes in peripheral airways induced by cigarette smoking.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells. Osteopontin (OPN) induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. To clarify the cooperative role of VEGF and OPN in tumor angiogenesis, we stained VEGF, OPN, and CD34 immunohistochemically in 87 cases of stage I non-small cell lung cancer (adenocarcinoma, 55, and squamous cell carcinoma, 32). Of the 87 patients studied, 27 patients had postoperative relapse and 60 patients did not. VEGF was found in 34 of 55 cases of adenocarcinomas and 14 of 32 squamous cell carcinomas, and OPN was found in 30 of 55 adenocarcinomas and 10 of 32 squamous cell carcinomas. In adenocarcinoma, microvessel counts of VEGF-positive and OPN-positive tumors were significantly higher than VEGF-negative and OPN-negative tumors, respectively, whereas in squamous cell carcinoma they were not. More importantly, patients with VEGF- and OPN-positive stage I lung adenocarcinoma had significantly worse prognosis as compared with other groups. Cooperation of OPN is important in VEGF-mediated tumor angiogenesis in stage I lung adenocarcinoma.

Clara cell 10 kilodalton protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and anti-inflammatory activity, and may play roles in controlling inflammation in the airway. This study was designed to examine immunohistochemical expression of CC10 in epithelial cells in small airways (perimeter < 6 mm) of asthmatic and control nonsmokers who underwent lung resection because of peripheral lung carcinoma and to compare CC10-positive epithelial cell proportions with numbers of inflammatory cells in small airways of asthmatics. Significantly decreased proportions of CC10-positive epithelial cells and significantly increased numbers of T cells, activated eosinophils, and mast cells in small airways of asthmatics were found compared with those of control subjects. CC10-positive epithelial cell proportions inversely correlated with numbers of T cells and mast cells in small airways of asthmatics. Decreases of CC10-producing cells may give an accelerating cause for further aggravation of inflammatory responses in chronic asthma.

Clara cell 10-kDa protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and antiinflammatory activity and may play a role in controlling airway inflammation. This study was designed to measure serum CC10 concentrations in healthy and asthmatic nonsmokers. Serum CC10 concentrations in asthmatic nonsmokers were significantly lower than in healthy nonsmokers. Asthmatic patients with a long duration of the disease (>/=10 years) had significantly lower serum CC10 levels than those with a short duration of the disease (<10 years). There was no significant difference in serum CC10 levels in asthmatic patients between the time of the asthmatic attack and the stable condition. Serum CC10 levels may reflect decreased production of CC10 caused by remodeling of the small airways in asthma.