title: Targeting of Porphyromonas gingivalis with a bispecific antibody directed to FcalphaRI (CD89) improves in vitro clearance by gingival crevicular neutrophils.
abstract: Phagocytosis and killing of pathogens by polymorphonuclear neutrophils (PMN) from gingival crevicular fluid (GCF) is diminished in chronic periodontitis patients. As an approach to improve targeting of PMN toward a periodontopathogen, Porphyromonas gingivalis, the efficacy of a bispecific antibody (BsAb) directed against both recombinant 130 kDa hemagglutinin domain (r130k-HMGD) of P. gingivalis, and PMN Fc receptor (FcR) was evaluated. GCF PMN exhibited higher IgA FcR (FcalphaRI) levels, and lower IgG FcR (FcgammaRIIa and FcgammaRIIIb) levels than PB PMN. Functional studies revealed that GCF PMN exhibited a higher capacity to phagocytose and kill P. gingivalis opsonized with a BsAb targeting P. gingivalis r130k-HMGD to FcalphaRI as compared to an anti-r130k-HMGD antibody. However, phagocytosis and killing activity of PB PMN that were incubated with the two antibodies proved comparable. These data support targeting of pathogens toward FcalphaRI as an option to improve antibacterial immunity in chronic periodontitis patients.
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan. kotetsuo@dent.niigata-u.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Ayano
authors.initials: A
authors.lastname: Takauchi
authors.forename: Annemiek B
authors.initials: AB
authors.lastname: van Spriel
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Vilé
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Shibata
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Abiko
authors.forename: Jan G J
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yoshie
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology / Q000627:therapeutic use*; D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D016866:Bacteroidaceae Infections / Q000628:therapy*; D005260:Female; D005883:Gingival Crevicular Fluid / Q000276:immunology / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D010587:Phagocytosis; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*
chemical_list: C117707:130k-HMGD protein, Porphyromonas gingivalis; D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D018033:Antibodies, Bispecific; D015703:Antigens, CD; C036832:Fc(alpha) receptor; D011961:Receptors, Fc