CYTOKINES FROM ACTIVATED T-CELLS INDUCE NORMAL ENDOTHELIAL-CELLS TO ACQUIRE THE PHENOTYPIC AND FUNCTIONAL FEATURES OF AIDS-KAPOSIS SARCOMA SPINDLE CELLS

被引：143

作者：

FIORELLI, V

GENDELMAN, R

SAMANIEGO, F

MARKHAM, PD

ENSOLI, B

机构：

[1] NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892

[2] ADV BIOSCI LABS INC,KENSINGTON,MD 20895

来源：

JOURNAL OF CLINICAL INVESTIGATION | 1995年 / 95卷 / 04期

关键词：

FVIII-RA; HIV-1; TAT PROTEIN; BFGF; ENDOTHELIAL CELL CYCLE; INFLAMMATORY CYTOKINES; AIDS;

D O I：

10.1172/JCI117849

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Kaposi's sarcoma (KS) is a proliferative disease of vascular origin particularly frequent in HIV-1-infected homosexual men (AIDS-KS) and characterized by proliferating spindle-shaped cells, angiogenesis, and inflammatory cell infiltration, Previous work has suggested that KS spindle cells are of endothelial cell origin and that chronic immune activation via the release of inflammatory cytokines may cooperate with basic fibroblast growth factor (bFGF) and the HIV-1 Tat protein in the induction and progression of AIDS-KS. Here we show that KS spindle cells have features of activated endothelial cells, and that conditioned media from activated T cells, rich in the same inflammatory cytokines increased in HIV-1-infected individuals, induce normal endothelial cells to acquire the phenotypic and functional features of KS cells, These include (a) acquisition of a similar pattern of cell surface antigen expression; (b) similar proliferative response to bFGF; (c) induction of the responsiveness to the mitogenic effect of extracellular HIV-1 Tat protein that is now able to promote the G1-S transition of endothelial cell cycle; and (d) induction in nude mice of vascular lesions closely resembling early KS as well as the lesions induced by inoculation of KS cells, These results suggest that chronic immune activation, via release of inflammatory cytokines, may play a role in the induction of KS.

引用

页码：1723 / 1734

页数：12

共 80 条

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