Intracellular and surface expression of the HIV-1 coreceptor CXCR4/fusin on various leukocyte subsets: rapid internalization and recycling upon activation.
We describe the expression and regulation of the HIV-1 coreceptor CXCR4/fusin. Using anti-CXCR4 mAb, we demonstrate that this chemokine receptor is highly expressed on neutrophils, monocytes, B cells, and naive T cells among peripheral blood cells. In secondary lymphoid organs CXCR4 was found to be expressed on B cells. However, individual variations with regard to surface expression could be observed on T cells. Expression of the receptor is not confined to the cell surface, as large amounts of intracellular stores can be found on various leukocytes. Upon activation with phorbol esters the amount of cell surface-expressed CXCR4 on lymphocytes increases twofold within 30 s before it is completely down-regulated within the next 2 min. Incubation of leukocytes with stroma derived factor-1alpha, the natural ligand for CXCR4, induces down-regulation of up to 60% of surface-expressed receptors in a pertussis toxin-insensitive manner. Interestingly, receptor cross-linking caused by incubation of cells with anti-CXCR4 mAb triggers receptor trafficking, in that the receptor is rapidly internalized and recycled to the cell surface. Therefore, receptor internalization and recycling may regulate the functional interaction of the receptor with envelope proteins during an initial step of HIV-1 infection.
Förster
R
R
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany. rfoerst@mdc-berlin.de
Kremmer
E
E
Schubel
A
A
Breitfeld
D
D
Kleinschmidt
A
A
Nerl
C
C
Bernhardt
G
G
Lipp
M
M
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism* / Q000821:virology; D051379:Mice; D009500:Neutralization Tests; D051381:Rats; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D015728:Receptors, HIV / Q000096:biosynthesis* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology
D000911:Antibodies, Monoclonal; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D013755:Tetradecanoylphorbol Acetate