DISTRIBUTION OF EXTRACELLULAR MATRICES, MATRIX RECEPTORS, AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN HUMAN AND EXPERIMENTAL LUNG GRANULOMATOUS INFLAMMATION

Aberrant deposition of extracellular matrices (ECMs) may affect lung i nflammation by influencing cell adhesion, migration, and activation. L ittle is known about the expression of ECMs in lungs with granulomatou s inflammation. Therefore, the authors investigated the distribution o f ECMs, matrix receptors of the integrin family, and transforming grow th factor-beta 1 (TGF-beta 1) in lungs from patients with pulmonary sa rcoidosis and animals with experimental granulomatosis. Immunohistoche mistry revealed increased deposition of type I collagen and fibronecti n in human lung granulomas when compared with healthy human lungs. Pro collagen type I and cellular fibronectin also were increased, suggesti ng local synthesis of ECM in sarcoid granulomas. These findings were a ccompanied by increased staining for fibronectin (alpha 5 beta 1) and collagen (alpha 2 beta 1) integrin receptors. The matrix-inducing cyto kine TGF-beta 1 was codistributed with the aforementioned molecules in the granulomas, whereas no significant staining for TGF-beta 1 was fo und in healthy lungs, Similar to sarcoid lungs, analysis of lung secti ons obtained from a murine model of granuloma formation revealed incre ased expression of fibronectin, collagen, integrin receptors, and TGF- beta 1 within granulomas. Based on these observations, there is increa sed expression of ECM and matrix receptors in both human and experimen tal lung granulomas. Such alterations may influence the recruitment an d activation of inflammatory cells and fibroblasts, promoting granulom a formation and remodeling of tissue by fibrosis. Activation of mononu clear cells resulting in production of TGF-beta 1 is likely to contrib ute to the changes described.