Title: Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection
Authors: Proost, Paul ×
De Meester, I
Schols, Dominique
Struyf, Sofie
Lambeir, A-M
Wuyts, Anja
Opdenakker, Ghislain
De Clercq, Erik
Scharpé, S
Van Damme, Jozef #
Issue Date: Mar-1998
Publisher: Amer soc biochemistry molecular biology inc
Series Title: Journal of Biological Chemistry vol:273 issue:13 pages:7222-7
Abstract: Chemokines are key players in inflammation and infection. Natural forms of the C-X-C chemokine granulocyte chemotactic protein-2 (GCP-2) and the C-C chemokine regulated on activation normal T cell expressed and secreted (RANTES), which miss two NH2-terminal residues, including a Pro in the penultimate position, have been isolated from leukocytes or tumor cells. In chemotaxis and intracellular calcium mobilization assays, the truncation caused a reduction in the specific activity of RANTES but not of GCP-2. The serine protease CD26/dipeptidyl-peptidase IV (CD26/DPP IV) could induce this observed NH2-terminal truncation of GCP-2 and RANTES but not that of the monocyte chemotactic proteins MCP-1, MCP-2 and MCP-3. No significant difference in neutrophil activation was detected between intact and CD26/DPP IV-truncated GCP-2. In contrast to intact natural RANTES(1-68), which still chemoattracts monocytes at 10 ng/ml, CD26/DPP IV-truncated RANTES(3-68) was inactive at 300 ng/ml and behaved as a natural chemotaxis inhibitor. Compared with intact RANTES, only a 10-fold higher concentration of RANTES(3-68) induced a significant Ca2+ response. Furthermore, RANTES(3-68) inhibited infection of mononuclear cells by an M-tropic HIV-1 strain 5-fold more efficiently than intact RANTES. Thus, proteolytic processing of RANTES by CD26/DPP IV may constitute an important regulatory mechanism during anti-inflammatory and antiviral responses.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Immunology (Rega Institute)
Academic Center for General Practice
Laboratory of Virology and Chemotherapy (Rega Institute)
Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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