title: The receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) is a new chemotactic factor for human monocytes.
abstract: Bone resorption is regulated by the immune system, where receptor activator of nuclear factor (NF)kappaB ligand (RANKL), a new member of the tumor-necrosis factor family, may contribute to pathological conditions. Due to the role of RANKL in the maturation of monocyte-derived osteoclasts, we hypothesized that RANKL could exert chemotactic properties toward monocytic cells. Our results demonstrate that RANKL induces the migration of MonoMac-6 monocytic cells as well as human freshly isolated total peripheral blood mononuclear cells (PBMC) and CD14+ purified PBMC. RANKL induces the migration of MonoMac-6 cells in a dose-dependent manner and with an efficacy similar to MCP-1. After an 8-h incubation, the soluble form of RANKL (sRANKL) started to exhibit a chemoattractive effect on MonoMac-6 cells, with an increased effect observed up to 24 h. RANKL elicits an additive chemotactic effect to MCP-1. Furthermore, addition of the RANKL decoy receptor osteoprotegerin in the lower well or RANKL in the upper well abrogates the RANKL-induced migration of MonoMac-6 cells, hallmarking a true specific activity. RNase protection assay experiments indicate that exposure of MonoMac-6 cells to RANKL had no significant effect on the expression of a variety of chemokines, known to attract monocytes. This study provides evidence that RANKL behaves as a chemotactic factor for monocytic cells, emphazing the cross-talk between bone and immune systems.
authors.affiliation: Unit INSERM 364, IFR 50 Faculté de Médecine Pasteur, Avenue de Valombrose 06107, Nice, Cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Breuil
authors.forename: Heidy
authors.initials: H
authors.lastname: Schmid-Antomarchi
authors.forename: Annie
authors.initials: A
authors.lastname: Schmid-Alliana
authors.forename: Roger
authors.initials: R
authors.lastname: Rezzonico
authors.forename: Liana
authors.initials: L
authors.lastname: Euller-Ziegler
authors.forename: Bernard
authors.initials: B
authors.lastname: Rossi
mesh_terms: D002352:Carrier Proteins / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D018448:Models, Immunological; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
chemical_list: D002352:Carrier Proteins; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human