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Natural truncation of RANTES abolishes signaling through the CC chemokine receptors CCR1 and CCR3, impairs its chemotactic potency and generates a CC chemokine inhibitor
Author(s) -
Struyf Sofie,
De Meester Ingrid,
Scharpé Simon,
Lenaerts JeanPierre,
Menten Patricia,
Wang Ji Ming,
Proost Paul,
Van Damme Jo
Publication year - 1998
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/(sici)1521-4141(199804)28:04<1262::aid-immu1262>3.0.co;2-g
Subject(s) - chemotaxis , ccl5 , chemokine , ccr3 , cc chemokine receptors , chemokine receptor , biology , ccr1 , macrophage inflammatory protein , ccl17 , monocyte , microbiology and biotechnology , chemokine receptor ccr5 , receptor , immunology , inflammation , t cell , biochemistry , immune system , il 2 receptor
Abstract Selective leukocyte trafficking towards sites of inflammation is mediated by chemokines. RANTES is a CC chemokine that attracts lymphocytes, monocytes, dendritic cells, eosinophils, basophils and NK cells. A natural form of human RANTES lacking two N‐terminal residues was isolated from stimulated sarcoma cells, fibroblasts, and leukocytes. RANTES(3 – 68) showed a more than tenfold reduction in chemotactic potency for monocytes and eosinophils. To elucidate the mechanism involved, receptor recognition studies were performed. In cells transfected with the CC chemokine receptor (CCR) 5, the major co‐receptor for macrophage‐tropic HIV‐1 strains, RANTES(3 – 68) mobilized calcium and desensitized RANTES(1 – 68)‐induced calcium fluxes equally well as RANTES(1 – 68). However, RANTES(3 – 68) was ineffective on CCR1 and CCR3 transfectants. The reduced potency of natural RANTES(3 – 68) by selective loss of receptor‐activating characteristics was confirmed with recombinant RANTES(3 – 68). In chemotaxis assays using monocytic cells, RANTES(3 – 68) inhibited RANTES(1 – 68), macrophage inflammatory protein‐1α (MIP‐1α), MIP‐1β or monocyte chemotactic protein‐3 (MCP‐3), but not MCP‐1‐ or MCP‐2‐induced chemotaxis. Thus, a minor post‐translational modification has a remarkable impact on the biological activities of RANTES and a pathophysiologically induced change in the relative amounts of intact and truncated RANTES might affect the outcome of inflammation or HIV infection.