scholarly journals Tat–Human Immunodeficiency Virus-1 Induces Human Monocyte Chemotaxis by Activation of Vascular Endothelial Growth Factor Receptor-1

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1365-1372 ◽  
Author(s):  
Stefania Mitola ◽  
Silvano Sozzani ◽  
Walter Luini ◽  
Luca Primo ◽  
Alessandro Borsatti ◽  
...  

Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti–VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody antiphosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1365-1372 ◽  
Author(s):  
Stefania Mitola ◽  
Silvano Sozzani ◽  
Walter Luini ◽  
Luca Primo ◽  
Alessandro Borsatti ◽  
...  

Abstract Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti–VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody antiphosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.


2021 ◽  
Vol 157 ◽  
pp. 103186
Author(s):  
Avash Das ◽  
Somnath Mahapatra ◽  
Dhrubajyoti Bandyopadhyay ◽  
Santanu Samanta ◽  
Sandipan Chakraborty ◽  
...  

Science ◽  
1992 ◽  
Vol 255 (5047) ◽  
pp. 989-991 ◽  
Author(s):  
C de Vries ◽  
J. Escobedo ◽  
H Ueno ◽  
K Houck ◽  
N Ferrara ◽  
...  

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1599-1601 ◽  
Author(s):  
Yoshiyasu Aoki ◽  
Robert Yarchoan ◽  
James Braun ◽  
Aikichi Iwamoto ◽  
Giovanna Tosato

Abstract Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked immunosorbent assay was developed for vIL-6 and applied to the study of PEL. Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL), it was not detectable in any of the control effusions. As expected, all PEL effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have previously been shown to induce vascular endothelial growth factor, which in turn can increase vascular permeability. The results of the current study suggest that these cytokines play a central role in the pathogenesis and manifestations of PEL.


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