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*
Pulmonary Center and
Department of Pathology, Boston University School of Medicine, Boston, MA 02188; and Boston Veterans Affairs Medical Center, Boston, MA 02130
Sarcoidosis is a systemic disease characterized by the accumulation of activated T cells and widespread granuloma formation. In addition, individual genetic predisposition appears to be important in this disease. Osteopontin, a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in the granulomas of tuberculosis, and is associated with genetic susceptibility to intracellular infection. The function of osteopontin in these T cell-mediated responses is unknown. We sought to elucidate the role of osteopontin in granulomatous inflammation by characterizing its expression in different stages of sarcoidosis and its effector function on T cells in vitro. Lymphocyte-associated expression of osteopontin in sarcoidosis was demonstrated by immunohistochemistry, and its expression correlated with granuloma maturity. In addition, osteopontin induced T cell chemotaxis, supported T cell adhesion (an effect enhanced by thrombin cleavage of osteopontin), and costimulated T cell proliferation. These results suggest a novel mechanism by which osteopontin and thrombin modulate T cell recruitment and activation in granulomatous inflammation.
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G. J. Nau, G. L. Chupp, J.-F. Emile, E. Jouanguy, J. S. Berman, J.-L. Casanova, and R. A. Young Osteopontin Expression Correlates with Clinical Outcome in Patients with Mycobacterial Infection Am. J. Pathol., July 1, 2000; 157(1): 37 - 42. [Abstract] [Full Text] [PDF]
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Y. Yokosaki, N. Matsuura, T. Sasaki, I. Murakami, H. Schneider, S. Higashiyama, Y. Saitoh, M. Yamakido, Y. Taooka, and D. Sheppard The Integrin alpha 9beta 1 Binds to a Novel Recognition Sequence (SVVYGLR) in the Thrombin-cleaved Amino-terminal Fragment of Osteopontin J. Biol. Chem., December 17, 1999; 274(51): 36328 - 36334. [Abstract] [Full Text] [PDF]
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R. Agnihotri, H. C. Crawford, H. Haro, L. M. Matrisian, M. C. Havrda, and L. Liaw Osteopontin, a Novel Substrate for Matrix Metalloproteinase-3 (Stromelysin-1) and Matrix Metalloproteinase-7 (Matrilysin) J. Biol. Chem., July 20, 2001; 276(30): 28261 - 28267. [Abstract] [Full Text] [PDF]
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