title: M-ficolin and leukosialin (CD43): new partners in neutrophil adhesion.
abstract: M-ficolin specificity for sialylated ligands prompted us to investigate its interactions with the main membrane sialoprotein of human neutrophils, CD43. rM-ficolin bound CD43 and prevented the access of anti-CD43 mAb. Moreover, rM-ficolin reacted exclusively with CD43 on Western blots of neutrophil lysate. We confirmed that M-ficolin is secreted by fMLP-activated neutrophils, and this endogenous M-ficolin also binds to CD43 and competes with anti-CD43 mAb. Anti-CD43 antibody cross-linking or fMLP resulted in M-ficolin and CD43 colocalization on polarized neutrophils. The binding of rM-ficolin to resting neutrophils induced cell polarization, adhesion, and homotypic aggregation as anti-CD43 mAb. The M-ficolin Y271F mutant, unable to bind sialic acid, neither reacted with neutrophils nor modulated their functions. Finally, rM-ficolin activated the lectin complement pathway on neutrophils. These results emphasize a new function of M-ficolin, different from ficolin pathogen recognition, i.e., a participation to neutrophil adhesion potentially important in early inflammation, as nanomolar agonist concentrations are sufficient to mobilize M-ficolin to the neutrophil surface. This multivalent lectin could then endow the antiadhesive CD43, essentially designed to prevent leukocyte aggregation in the blood flow, with new adhesive properties and explain, at least in part, dual-adhesive/antiadhesive roles of CD43 in neutrophil recruitment.
authors.affiliation: Batiment Lavoisier, Hôpital Necker, 149 rue de Sevres, Paris, France.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Moreno-Amaral
authors.forename: Evelyne
authors.initials: E
authors.lastname: Gout
authors.forename: Claudia
authors.initials: C
authors.lastname: Danella-Polli
authors.forename: Fanny
authors.initials: F
authors.lastname: Tabarin
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesavre
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pereira-da-Silva
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Thielens
authors.forename: Lise
authors.initials: L
authors.lastname: Halbwachs-Mecarelli
mesh_terms: D002448:Cell Adhesion / Q000276:immunology*; D003167:Complement Activation / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000276:immunology / Q000378:metabolism*; D051917:Leukosialin / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D000097604:Ficolins
chemical_list: D037102:Lectins; D051917:Leukosialin; D019158:N-Acetylneuraminic Acid; D000097604:Ficolins