Monocyte-derived dendritic cells and monocytes migrate to HIV-Tat RGD and basic peptides.
OBJECTIVE
Extracellular Tat released from HIV-1-infected cells is a mitogenic and motogenic factor for endothelial and Kaposi's sarcoma (KS)-derived cells and is angiogenic in vivo. Here we show for the first time that Tat induces migration of human dendritic cells in a concentration-dependent manner and that the Arg-Gly-Asp (RGD) and basic Tat peptides contribute to dendritic and monocyte cell migration. In vivo, Tat stimulates invasion of macrophages into a matrigel sponge.


METHODS
Monocyte and dendritic cell chemotaxis was assessed using the Boyden chamber assay.


RESULTS
Tat induced migration of monocyte-derived dendritic cells at the same levels as the N-formyl-Met-Leu-Phe peptide, and of monocytes at levels comparable to RANTES. Peptide mapping of the chemotactic activity of Tat showed that the RGD domain, which has been shown to support integrin-mediated cell migration, and the basic domain which binds and activates the tyrosine kinase receptor KDR on endothelial cells, both had activity. Antibody-blocking experiments indicate that responses to the RGD domain was inhibited by beta1 and alpha vbeta3 integrin blocking antibodies. Combination of the Tat RGD and basic peptides did not show additive effects; however, Tat co-operated with macrophage-chemotactic protein or RANTES in inducing monocyte migration.


CONCLUSIONS
Our results show that Tat can act as a chemoattractant for dendritic cells, and that both the RGD and basic domains are involved in this response. These same domains attract monocytes. The alpha vbeta3 and beta1 integrins are equally involved in Tat-induced monocyte migration, while the alpha vbeta3 integrin largely mediates the dendritic cell response to Tat.
Benelli
R
R
Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Mortarini
R
R
Anichini
A
A
Giunciuglio
D
D
Noonan
D M
DM
Montalti
S
S
Tacchetti
C
C
Albini
A
A
D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000166:cytology*; D015696:Gene Products, tat; D006801:Humans; D009000:Monocytes / Q000166:cytology*; D009842:Oligopeptides
D015696:Gene Products, tat; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid