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用一种针对FcalphaRI(CD89)的双特异性抗体靶向牙龈卟啉单胞菌可提高龈沟中性粒细胞的体外清除率。

Targeting of Porphyromonas gingivalis with a bispecific antibody directed to FcalphaRI (CD89) improves in vitro clearance by gingival crevicular neutrophils.

作者信息

Kobayashi Tetsuo, Takauchi Ayano, van Spriel Annemiek B, Vilé Henriette A, Hayakawa Mitsuo, Shibata Yasuko, Abiko Yoshimitsu, van de Winkel Jan G J, Yoshie Hiromasa

机构信息

Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.

出版信息

Vaccine. 2004 Dec 16;23(5):585-94. doi: 10.1016/j.vaccine.2004.07.015.

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.

摘要

慢性牙周炎患者龈沟液(GCF)中的多形核中性粒细胞(PMN)对病原体的吞噬和杀伤作用减弱。作为一种提高PMN对牙周病原体牙龈卟啉单胞菌靶向性的方法,评估了一种双特异性抗体(BsAb)的疗效,该抗体针对牙龈卟啉单胞菌的重组130 kDa血凝素结构域(r130k-HMGD)和PMN Fc受体(FcR)。与外周血PMN(PB PMN)相比,GCF PMN表现出更高的IgA FcR(FcalphaRI)水平和更低的IgG FcR(FcgammaRIIa和FcgammaRIIIb)水平。功能研究表明,与抗r130k-HMGD抗体相比,GCF PMN对用靶向牙龈卟啉单胞菌r130k-HMGD至FcalphaRI的BsAb调理的牙龈卟啉单胞菌具有更高的吞噬和杀伤能力。然而,用这两种抗体孵育的PB PMN的吞噬和杀伤活性相当。这些数据支持将病原体靶向FcalphaRI作为改善慢性牙周炎患者抗菌免疫的一种选择。

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