title: Cytokines from activated T cells induce normal endothelial cells to acquire the phenotypic and functional features of AIDS-Kaposi's sarcoma spindle cells.
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.
authors.affiliation: Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: V
authors.initials: V
authors.lastname: Fiorelli
authors.forename: R
authors.initials: R
authors.lastname: Gendelman
authors.forename: F
authors.initials: F
authors.lastname: Samaniego
authors.forename: P D
authors.initials: PD
authors.lastname: Markham
authors.forename: B
authors.initials: B
authors.lastname: Ensoli
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000473:pathology; D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005169:Factor VIII / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D016193:G1 Phase / Q000502:physiology; D015696:Gene Products, tat / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008819:Mice, Nude; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D012514:Sarcoma, Kaposi / Q000150:complications / Q000209:etiology* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*; D014471:Umbilical Veins; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D016207:Cytokines; D015696:Gene Products, tat; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D016222:Fibroblast Growth Factor 2; D012313:RNA; D005169:Factor VIII