Role of galectin-3 in human pulmonary fibrosis.

BACKGROUND: Galectin-3 is a beta-galactoside-binding protein which is implicated in diverse physiological and pathological processes including human liver cirrhosis and a mouse lung fibrosis model. The aim of this study is to determine whether galectin-3 is involved in human lung fibrosis. METHODS: We measured galectin-3 concentration in bronchoalveolar lavage fluid (BALF) and examined its expression in alveolar macrophages from patients with interstitial lung disorders using ELISA and immunohistochemical staining, respectively. Using monocyte/macrophage cell lines in vitro, we examined the effect of cytokines on galectin-3 expression, and the opposite similarly by RT-PCR and Western blotting. Finally, we performed Micro Boyden chamber assay and Sircoll assay to determine whether galectin-3 induces migration and collagen synthesis, respectively, in fibroblasts. RESULTS: Galectin-3 was specifically increased in BALF from patients with idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia associated with collagen vascular disease (CVD-IP). Galectin-3 levels in BALF seemed to be lower in IPF and CVD-IP patients receiving corticosteroid therapy. Alveolar macrophages from IPF patients expressed more galectin-3 compared with those from control. Galectin-3 expression was induced by tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-gamma in a monocytic cell line U937. Galectin-3 also induced mRNA expression and protein production of TNF-alpha and interleukin (IL)-8 in a macrophage cell line THP-1. This lectin stimulated NIH-3T3 fibroblast to induce migration and collagen synthesis in vitro. CONCLUSIONS: These results suggest that galectin-3 is involved in the pathogenesis of human IPF and CVD-IP by activating macrophages and fibroblasts.

[A case of interstitial pneumonia accompanying SIADH].

A 75-year-old man was transferred to our hospital on November 28, 2003 because of acute aggravation while being treated for interstitial pneumonia superimposed on pneumoconiosis at a local hospital. Upon admission, oxygen inhalation therapy and antimicrobial chemotherapy were started for the interstitial pneumonia. In addition, since he showed hyponatremia from admission, a saline load was administered and the clinical course was observed. However, disturbance of consciousness developed on January 5, 2004. At that time, the serum sodium was 115mEq/l. Since secretion of antidiuretic hormone (SIADH) had continued despite a low plasma osmolarity, we diagnosed syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We initiated treatment with water restriction and saline load, but no remarkable improvement was observed. From February 7, 40mg /day prednisolone was started because of aggravation of interstitial pneumonia. As a result, the respiratory status and image findings improved, and serum sodium level was normalized. This case was considered to be SIADH secondary to interstitial pneumonia. Among respiratory tract diseases, SIADH is often caused by small cell lung carcinoma, although it may also occur concurrently with other respiratory tract diseases. Since hyponatremia may manifest grave disturbance of consciousness, investigation of the cause is important.