Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6

被引:309
作者
Aoki, Y
Jaffe, ES
Chang, Y
Jones, K
Teruya-Feldstein, J
Moore, PS
Tosato, G
机构
[1] US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA
[2] NCI, Hematopathol Sect, NIH, Bethesda, MD USA
[3] Columbia Univ, Sch Publ Hlth, Dept Pathol, New York, NY USA
关键词
D O I
10.1182/blood.V93.12.4034.412k38_4034_4043
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and murine IL-6, The biological activities of vIL-6 are largely unknown. To gain insight into the biology of vIL-6, we expressed vIL-6 in murine fibroblasts NIH3T3 cells and inoculated stable vIL-6-producing clones into athymic mice. vIL-6 was detected selectively in the blood of mice injected with vIL-6-expressing clones. Compared with controls, vIL-6-positive mice displayed increased hematopoiesis in the myeloid, erythroid, and megakaryocytic lineages; plasmacytosis in spleen and lymph nodes; hepatosplenomegaly; and polyclonal hypergammaglobulinemia, vIL-6-expressing NIH3T3 cells gave rise to tumors more rapidly than did control cells, and vIL-6-positive tumors were more vascularized than controls. Vascular endothelial growth factor (VEGF) was detected at higher levels in the culture supernatant of vIL-6-expressing cells compared with controls, and immunohistochemical staining detected VEGF in spleen, lymph nodes, and tumor tissues from mice bearing vIL-6-producing tumors but not control tumors. Thus, vIL-6 is a multifunctional cytokine that promotes hematopoiesis, plasmacytosis, and angiogenesis, Through these functions, vIL-6 may play an important role in the pathogenesis of certain KSHV-associated disorders. (C) 1999 by The American Society of Hematology.
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页码:4034 / 4043
页数:10
相关论文
共 51 条
[1]   HUMAN INTERFERON-INDUCIBLE PROTEIN-10 IS A POTENT INHIBITOR OF ANGIOGENESIS IN-VIVO [J].
ANGIOLILLO, AL ;
SGADARI, C ;
TAUB, DD ;
LIAO, F ;
FARBER, JM ;
MAHESHWARI, S ;
KLEINMAN, HK ;
REAMAN, GH ;
TOSATO, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (01) :155-162
[2]   Mechanisms of growth control of Kaposi's sarcoma-associated herpes virus-associated primary effusion lymphoma cells [J].
Asou, H ;
Said, JW ;
Yang, R ;
Munker, R ;
Park, DJ ;
Kamada, N ;
Koeffler, HP .
BLOOD, 1998, 91 (07) :2475-2481
[3]   G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator [J].
Bais, C ;
Santomasso, B ;
Coso, O ;
Arvanitakis, L ;
Raaka, EG ;
Gutkind, JS ;
Asch, AS ;
Cesarman, E ;
Gerhengorn, MC ;
Mesri, EA .
NATURE, 1998, 391 (6662) :86-89
[4]   MODULATION OF MEGAKARYOCYTOPOIESIS BY THROMBOPOIETIN - THE C-MPL LIGAND [J].
BANU, N ;
WANG, JF ;
DENG, BJ ;
GROOPMAN, JE ;
AVRAHAM, H .
BLOOD, 1995, 86 (04) :1331-1338
[5]   Multiple myeloma [J].
Bataille, R ;
Harousseau, JL .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (23) :1657-1664
[6]   ALLEVIATION OF SYSTEMIC MANIFESTATIONS OF CASTLEMANS DISEASE BY MONOCLONAL ANTI-INTERLEUKIN-6 ANTIBODY [J].
BECK, JT ;
HSU, SM ;
WIJDENES, J ;
BATAILLE, R ;
KLEIN, B ;
VESOLE, D ;
HAYDEN, K ;
JAGANNATH, S ;
BARLOGIE, B .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (09) :602-605
[7]   Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal [J].
Benjamin, LE ;
Golijanin, D ;
Itin, A ;
Pode, D ;
Keshet, E .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (02) :159-165
[8]   Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines [J].
Boshoff, C ;
Endo, Y ;
Collins, PD ;
Takeuchi, Y ;
Reeves, JD ;
Schweickart, VL ;
Siani, MA ;
Sasaki, T ;
Williams, TJ ;
Gray, PW ;
Moore, PS ;
Chang, Y ;
Weiss, RA .
SCIENCE, 1997, 278 (5336) :290-294
[9]   KAPOSIS SARCOMA-ASSOCIATED HERPESVIRUS INFECTS ENDOTHELIAL AND SPINDLE CELLS [J].
BOSHOFF, C ;
SCHULZ, TF ;
KENNEDY, MM ;
GRAHAM, AK ;
FISHER, C ;
THOMAS, A ;
MCGEE, JO ;
WEISS, RA ;
OLEARY, JJ .
NATURE MEDICINE, 1995, 1 (12) :1274-1278
[10]   DYSREGULATED INTERLEUKIN-6 EXPRESSION PRODUCES A SYNDROME RESEMBLING CASTLEMANS DISEASE IN MICE [J].
BRANDT, SJ ;
BODINE, DM ;
DUNBAR, CE ;
NIENHUIS, AW .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (02) :592-599