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Cytokines from activated T cells induce normal endothelial cells to acquire the phenotypic and functional features of AIDS-Kaposi's sarcoma spindle cells.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 1995 Apr; Vol. 95 (4), pp. 1723-34. - Publication Year :
- 1995
-
Abstract
- 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.
- Subjects :
- Acquired Immunodeficiency Syndrome pathology
Animals
Antigens, Differentiation, Myelomonocytic biosynthesis
Biomarkers
Cell Adhesion Molecules biosynthesis
Culture Media, Conditioned pharmacology
Endothelium, Vascular pathology
Factor VIII biosynthesis
Fibroblast Growth Factor 2 pharmacology
G1 Phase physiology
Gene Products, tat pharmacology
Humans
Lymphocyte Activation
Mice
Mice, Nude
Platelet Endothelial Cell Adhesion Molecule-1
Protein Biosynthesis
RNA biosynthesis
Sarcoma, Kaposi complications
Sarcoma, Kaposi pathology
Umbilical Veins
tat Gene Products, Human Immunodeficiency Virus
Acquired Immunodeficiency Syndrome complications
Cytokines pharmacology
Endothelium, Vascular drug effects
Sarcoma, Kaposi etiology
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 95
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 7535796
- Full Text :
- https://doi.org/10.1172/JCI117849