The Role of Mig, the Monokine Induced by Interferon-γ, and IP-10, the Interferon-γ–Inducible Protein-10, in Tissue Necrosis and Vascular Damage Associated With Epstein-Barr Virus-Positive Lymphoproliferative Disease

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Abstract
The mechanisms of tissue necrosis and vascular damage characteristics of certain Epstein-Barr virus (EBV)-associated lymphoproliferative disorders are unknown. The CXC chemokines interferon-γ–inducible protein-10 (IP-10) and the monokine induced by interferon-γ (Mig) caused tissue necrosis and vascular damage in Burkitt's lymphoma tumors established in nude mice. We report higher levels of IP-10 and Mig gene expression in tissues with necrosis and vascular damage from EBV-positive lymphomatoid granulomatosis and nasal or nasal-type T/natural killer (NK)-cell lymphomas compared with tissues with lymphoid hyperplasia, which lacked tissue necrosis and vascular damage. By immunohistochemistry, Mig and IP-10 proteins localized with similar patterns in viable tissue surrounding dead tissue, mostly within endothelial cells, monocyte/macrophages, and lymphocytes. Circulating levels of IP-10 were abnormally elevated in patients with EBV-positive lymphomatoid granulomatosis and nasal or nasal-type T/NK-cell lymphomas. These experiments provide the first description of the presence of Mig in any human normal or diseased tissue and the first description of IP-10 in certain lymphoproliferative lesions. These data suggest that Mig and IP-10 play an important role in the pathogenesis of tissue necrosis and vascular damage associated with certain EBV-positive lymphoproliferative processes.