title: LPS induces pulp progenitor cell recruitment via complement activation.
abstract: Complement system, a major component of the natural immunity, has been recently identified as an important mediator of the dentin-pulp regeneration process through STRO-1 pulp cell recruitment by the C5a active fragment. Moreover, it has been shown recently that under stimulation with lipoteichoic acid, a complex component of the Gram-positive bacteria cell wall, human pulp fibroblasts are able to synthesize all proteins required for complement activation. However, Gram-negative bacteria, which are also involved in tooth decay, are known as powerful activators of complement system and inflammation. Here, we investigated the role of Gram-negative bacteria-induced complement activation on the pulp progenitor cell recruitment using lipopolysaccharide (LPS), a major component of all Gram-negative bacteria. Our results show that incubating pulp fibroblasts with LPS induced membrane attack complex formation and C5a release in serum-free fibroblast cultures. The produced C5a binds to the pulp progenitor cells' membrane and induces their migration toward the LPS stimulation chamber, as revealed by the dynamic transwell migration assays. The inhibition of this migration by the C5aR-specific antagonist W54011 indicates that the pulp progenitor migration is mediated by the interaction between C5a and C5aR. Our findings demonstrate, for the first time, a direct interaction between the recruitment of progenitor pulp cells and the activation of complement system generated by pulp fibroblast stimulation with LPS.
authors.affiliation: Aix Marseille Université, CNRS, ISM UMR 7287, Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Chmilewsky
authors.affiliation: Aix Marseille Université, CNRS, ISM UMR 7287, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Jeanneau
authors.affiliation: Aix Marseille Université, CNRS, ISM UMR 7287, Marseille, France APHM, Hôpital Timone, Service d'Odontologie, Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Laurent
authors.affiliation: Aix Marseille Université, CNRS, ISM UMR 7287, Marseille, France imad.about@univ-amu.fr.
authors.forename: I
authors.initials: I
authors.lastname: About
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D018929:Cell Culture Techniques; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects*; D003167:Complement Activation / Q000187:drug effects*; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000187:drug effects; D003731:Dental Caries / Q000382:microbiology; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000037:antagonists & inhibitors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors; D013234:Stem Cells / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; C488033:C5AR1 protein, human; D002630:Chemotactic Factors; D015938:Complement Membrane Attack Complex; D007155:Immunologic Factors; D008070:Lipopolysaccharides; C470794:N-((4-dimethylaminophenyl)methyl)-N-(4-isopropylphenyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-1-carboxamide; D044087:Receptor, Anaphylatoxin C5a; D013764:Tetrahydronaphthalenes; D015936:Complement C5a
keywords: caries; chemotaxis; complement C5a; pulp biology; regeneration; stem cell(s)