title: The role of Mig, the monokine induced by interferon-gamma, and IP-10, the interferon-gamma-inducible protein-10, in tissue necrosis and vascular damage associated with Epstein-Barr virus-positive lymphoproliferative disease.
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-gamma-inducible protein-10 (IP-10) and the monokine induced by interferon-gamma (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.
authors.affiliation: Laboratory of Pathology, Hematopathology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1500, USA.
authors.forename: J
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: E S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: P R
authors.initials: PR
authors.lastname: Burd
authors.forename: H
authors.initials: H
authors.lastname: Kanegane
authors.forename: D W
authors.initials: DW
authors.lastname: Kingma
authors.forename: W H
authors.initials: WH
authors.lastname: Wilson
authors.forename: D L
authors.initials: DL
authors.lastname: Longo
authors.forename: G
authors.initials: G
authors.lastname: Tosato
mesh_terms: D000328:Adult; D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000096:biosynthesis*; D019743:Chemokines, CXC; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006566:Herpesviridae Infections / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009336:Necrosis; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology* / Q000821:virology
chemical_list: C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma