Seiji Fujioka

Evaluation of serum KL-6 levels in patients with pulmonary tuberculosis

SETTING KL-6, a human MUC-1 mucin preferentially expressed on type II pneumocytes, is a sensitive serum marker for evaluating alveolar damage of interstitial pneumonia and pulmonary fibrosis. Some patients with pulmonary tuberculosis develop severe respiratory dysfunction caused by extensive pulmonary fibrosis, compensatory emphysema and fibrous pleural thickening. OBJECTIVE To evaluate the clinico-pathological significance of KL-6 in pulmonary tuberculosis. DESIGN Serum KL-6 levels were measured in sera from 57 patients with active pulmonary tuberculosis and 38 healthy controls by a sandwich-type enzyme-linked immunosorbent assay. Immunohistochemistry was performed by an avidin-biotin-peroxidase complex method. RESULTS KL-6 levels were significantly higher in the patients than in the healthy controls (518 +/- 693 [SD] vs 227 +/- 91 U/ml, P < 0.001) and increased significantly according to the extent of pulmonary lesions evaluated by chest X-ray (P < 0.001). There was a significant negative correlation between serum KL-6 levels and % vital capacity (VC) (r = 0.642, P < 0.05). KL-6 was strongly expressed on proliferated type II pneumocytes and cuboidal epithelial cells adjacent to thickened intralobular septa and pleura. CONCLUSIONS In pulmonary tuberculosis, serum KL-6 originates from proliferated type II pneumocytes and cuboidal epithelial cells, and is a useful marker presenting the degree and extent of pulmonary fibroproductive lesions.

Evaluation of soluble IL-6 receptor concentration in serum and epithelial lining fluid from patients with interstitial lung diseases.

We measured soluble IL‐6 receptor (sIL‐6R) levels in serum and bronchoalveolar lavage fluids (BALF) from patients with interstitial pneumonia of unknown etiology (IP) (n= 17), sarcoidosis (n= 8) and normal control subjects (n= 10), to investigate its role in pulmonary diseases. Soluble IL‐6R was determined by an ELISA. The volume of epithelial lining fluid (ELF) in BALF was estimated using an urea method. We found that levels of sIL‐6R in serum, BALF, and ELF from patients with IP or sarcoidosis were significantly higher than those from normal subjects. Furthermore, levels of sIL‐6R in BALF or ELF were significantly correlated with those of albumin, indicating that sIL‐6R, together with albumin, may enter ELF as a result of the increased permeability caused by pulmonary inflammation. Thus most of the sIL‐6R in ELF would be from serum, and relatively small amounts of it might be produced locally. However, sIL‐6R levels in ELF, but neither serum nor BALF, were significantly correlated with levels of C‐reactive protein in patients with IP. These results suggest that both systemic and local production of sIL‐6R are increased, and raised sIL‐6R is involved in the modulation of systemic and local inflammatory responses in patients with IP and sarcoidosis.

Ubenimex Activates the E-Cadherin-mediated Adhesion of a Breast Cancer Cell Line YMB-S

It has been reported that ubenimex, a biological response modifier, has a direct anti‐tumor effect. To clarify the mechanism involved, we examined the effects of ubenimex on the growth and adhesive property of a breast cancer cell line YMB‐S. The cells proliferate in a floating manner without aggregation in normal complete medium. Ubenimex induced cell‐cell and cell‐surface adhesion of the cells accompanied with growth suppression. E‐Cadherin localized at cell‐cell contact sites of adhered cells, and anti‐E‐cadherin antibody inhibited the adhesion. Both Western blot analysis and binding assay disclosed that there was no apparent difference between E‐cadherin levels of the cells before and after the treatment with ubenimex. These results indicate that ubenimex inhibits the proliferation of YMB‐S cells and augments cell‐to‐cell adhesion through the induction of E‐cadherin ‐mediated adhesion resulting from the functional activation of pre‐expressed but inefficient E‐cadherin.