Infection with human immunodeficiency virus-1 increases expression of vascular endothelial cell growth factor in T cells: implications for acquired immunodeficiency syndrome-associated vasculopathy.
Alterations in the vascular system and the onset of angioproliferative lesions such as Kaposi's sarcoma (KS) are common traits of human immunodeficiency virus-1 (HIV-1)-infected patients. To investigate possible factors involved in acquired immunodeficiency syndrome (AIDS)-associated vasculopathy and vascular malfunction, expression of vascular endothelial cell growth factor-A (VEGF-A) was analyzed in HUT 78 T lymphocytes upon infection with HIV-1. VEGF-A was found to be increased in supernatants from infected cells as compared with uninfected cells. In addition, VEGF-A mRNA expression and protein secretion were significantly increased in HUT 78 cells incubated with conditioned medium (CM) derived from HIV-1 chronically infected HUT 78 cells (HIV-TCM) as compared with CM from uninfected cells (TCM). Increase of VEGF-A production in T cells was promoted by inflammatory cytokines (IC) present in HIV-TCM, including tumor necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin-1beta (IL-1beta), and IL-6. These IC that have been shown to be increased in sera of HIV-1-infected patients and to be increased by HIV-1 infection or cell activation in these individuals as well as HIV-TCM also increased VEGF-A expression in primary T lymphocytes. Consistent with this, VEGF-A concentrations were found to be higher in sera of HIV-1-infected patients with (mean, 357.1 +/- 197.9 pg/mL) and without KS (mean, 256.7 +/- 137.5 pg/mL) as compared with uninfected individuals (mean, 188.6 +/- 91.7 pg/mL). These data suggest that increased secretion of VEGF-A by T lymphocytes of HIV-1-infected individuals may induce vascular leakage and stimulate proliferation of vascular endothelial cells, which are hallmarks of AIDS-associated vasculopathy and especially of KS development.
Ascherl
G
G
Department of Virology, Max Planck Institute for Biochemistry, Martinsried, Germany.
Hohenadl
C
C
Schatz
O
O
Shumay
E
E
Bogner
J
J
Eckhart
L
L
Tschachler
E
E
Monini
P
P
Ensoli
B
B
Stürzl
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000150:complications; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D015153:Blotting, Western; D002460:Cell Line; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000097:blood / Q000235:genetics*; D015870:Gene Expression; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood; D012514:Sarcoma, Kaposi / Q000097:blood / Q000150:complications; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors