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Title: NH2- and COOH-terminal truncations of murine granulocyte chemotactic protein-2 augment the in vitro and in vivo neutrophil chemotactic potency
Authors: Wuyts, Anja ×
D'Haese, A
Cremers, V
Menten, Patricia
Lenaerts, J-P
De Loof, Arnold
Heremans, Hubertine
Proost, Paul
Van Damme, Jozef #
Issue Date: Dec-1999
Series Title: Journal of Immunology vol:163 issue:11 pages:6155-63
Abstract: Chemokines are important mediators of leukocyte migration during the inflammatory response. Post-translational modifications affect the biological potency of chemokines. In addition to previously identified NH2-terminally truncated forms, COOH-terminally truncated forms of the CXC chemokine murine granulocyte chemotactic protein-2 (GCP-2) were purified from conditioned medium of stimulated fibroblasts. The truncations generated 28 natural murine GCP-2 isoforms containing 69-92 residues, including most intermediate forms. Both NH2- and COOH-terminal truncations of GCP-2 resulted in enhanced chemotactic potency for human and murine neutrophils in vitro. The truncated isoform GCP-2(9-78) was 30-fold more potent than intact GCP-2(1-92)/LPS-induced CXC chemokine (LIX) at inducing an intracellular calcium increase in human neutrophils. After intradermal injection in mice, GCP-2(9-78) was also more effective than GCP-2(1-92)/LIX at inducing neutrophil infiltration. Similar to human IL-8 and GCP-2, murine GCP-2(9-78) and macrophage inflammatory protein-2 (MIP-2) induced calcium increases in both CXCR1 and CXCR2 transfectants. Murine GCP-2(9-78) could desensitize the calcium response induced by MIP-2 in human neutrophils and vice versa. Furthermore, MIP-2 and truncated GCP-2(9-78), but not intact GCP-2(1-92)/LIX, partially desensitized the calcium response to human IL-8 in human neutrophils. Taken together, these findings point to an important role of post-translationally modified GCP-2 to replace IL-8 in the mouse.
URI: 
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Academic Center for General Practice
Laboratory of Molecular Immunology (Rega Institute)
Laboratory of Immunobiology (Rega Institute)
Department of Biology - miscellaneous
× corresponding author
# (joint) last author

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