title: Chemokines synergize in the recruitment of circulating neutrophils into inflamed tissue.
abstract: The innate immune response against micro-organisms is mediated by phagocytes, attracted by chemokines and other G protein-coupled receptor (GPCR) ligands. Originally, we observed increased neutrophil migration by the interaction of inflammatory CXC chemokines such as IL-8/CXCL8 and granulocyte chemotactic protein (GCP)-2/CXCL6 with regakine-1, a CC chemokine constitutively present in plasma. We here demonstrate statistically significant synergy between regakine-1 and the neutrophil attractants C5a or IL-8/CXCL8 in inducing neutrophil shape change and migration under agarose. In addition, regakine-1 attracted human bone marrow granulocytes and enhanced their chemotactic response to IL-8/CXCL8 in a dose-dependent manner. Thus, plasma chemokines may regulate the number of circulating leukocytes under homeostatic conditions and may facilitate extra recruitment of bone marrow neutrophils during inflammation. Indeed, in vivo, regakine-1 provoked a mild neutrophilia in rabbits upon intravenous injection. We also observed that the CC chemokines regakine-1 and monocyte chemotactic protein-3/CCL7 as well as the CXC chemokine stromal cell-derived factor-1alpha/CXCL12 co-operated with murine GCP-2 after intraperitoneal co-administration to increase neutrophil influx in mice. These data demonstrate that inducible and constitutive GPCR ligands synergize to enhance inflammation and facilitate a more effective immune response.
authors.affiliation: Laboratory of Molecular Immunology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Struyf
authors.forename: Mieke
authors.initials: M
authors.lastname: Gouwy
authors.forename: Chris
authors.initials: C
authors.lastname: Dillen
authors.forename: Paul
authors.initials: P
authors.lastname: Proost
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011817:Rabbits
chemical_list: D018925:Chemokines