Hellwig S M, van Oirschot H F, Hazenbos W L, van Spriel A B, Mooi F R, van De Winkel J G
Laboratory for Infectious Diseases. National Institute of Public Health and the Environment, Bilthoven, Utrecht, The Netherlands.
J Infect Dis. 2001 Mar 15;183(6):871-9. doi: 10.1086/319266. Epub 2001 Feb 13.
In the absence of opsonizing antibodies, Bordetella pertussis, the causative agent of pertussis, readily binds to phagocytes via complement receptor 3 (CR3). After opsonization with antibodies, binding is mediated by IgG receptors (FcgammaR). The effect of targeting B. pertussis to either FcgammaR or CR3 was studied. The fate of unopsonized B. pertussis, IgG-opsonized B. pertussis, and B. pertussis opsonized with bispecific antibodies (BsAbs) directed to CR3 or FcgammaRII/-III was compared. IgG antibodies mediated binding and phagocytosis of B. pertussis via FcgammaR by polymorphonuclear leukocytes (PMNL) in vitro. Opsonization of B. pertussis with BsAbs directed against either CR3 or FcgammaRII/-III facilitated PMNL phagocytosis; however, in vivo studies with BsAb revealed that FcgammaR-mediated uptake facilitates B. pertussis clearance, in contrast to uptake via CR3. Targeting of B. pertussis to FcgammaRII/-III in mice deficient in FcgammaRII or FcgammaRIII indicated that the protective effect is attributable to FcgammaRIII. Competition between uptake via CR3 or FcgammaR may determine the outcome of natural infection.
在缺乏调理素抗体的情况下，百日咳的病原体百日咳博德特氏菌可通过补体受体3（CR3）轻易地与吞噬细胞结合。用抗体进行调理后，结合由IgG受体（FcγR）介导。研究了将百日咳博德特氏菌靶向FcγR或CR3的效果。比较了未调理的百日咳博德特氏菌、IgG调理的百日咳博德特氏菌以及用针对CR3或FcγRII / -III的双特异性抗体（BsAb）调理的百日咳博德特氏菌的命运。IgG抗体在体外通过多形核白细胞（PMNL）介导百日咳博德特氏菌通过FcγR的结合和吞噬作用。用针对CR3或FcγRII / -III的BsAb对百日咳博德特氏菌进行调理可促进PMNL吞噬作用；然而，用BsAb进行的体内研究表明，与通过CR3摄取相比，FcγR介导的摄取有助于清除百日咳博德特氏菌。在缺乏FcγRII或FcγRIII的小鼠中将百日咳博德特氏菌靶向FcγRII / -III表明，保护作用归因于FcγRIII。通过CR3或FcγR摄取之间的竞争可能决定自然感染的结果。
