High serum levels of thrombospondin-1 in patients with idiopathic interstitial pneumonia

Thrombospondin-1 (TSP-1), a multifunctional matricellular glycoprotein, can activate transforming growth factor-beta, an important profibrotic cytokine involved in various fibrotic diseases. TSP-1 is expressed in the lung tissue of animal models of bleomycin-induced pulmonary fibrosis and in patients with some interstitial lung diseases. The present study investigated the serum and bronchoalveolar lavage fluid (BALF) levels of TSP-1 in the idiopathic interstitial pneumonias (IIPs) and the relationship between these levels and other clinical. factors. The TSP-1 in the serum and BALF were measured in 45 patients with pathologically diagnosed IIPs [22 with usual interstitial pneumonia (UIP), 23 patients with non-specific interstitial. pneumonia (NSIP)], as well as in 28 patients with pulmonary sarcoidosis and 15 healthy volunteers using a competitive enzyme immunoassay. The expression and localization of TSP-1 in the lungs were analyzed by immunohistochemical staining. The serum TSP-1 levels were significantly higher in patients with IIPs than in either those with sarcoidosis or the controls. These levels correlated well with those of an angiogenic cytokine vascular endothelial growth factor while correlating inversely with the %VC. Positive immunostaining of TSP-1 was predominantly observed in the regenerated alveolar epithelium and alveolar macrophages in the lung. Our findings suggest that the circulating TSP-1 levels are associated with the presence of interstitial pneumonia, but further studies are required before we can definitively conclude that TSP-1 plays a role in the pathogenesis of these diseases. (C) 2008 Elsevier Ltd. All rights reserved.