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首页> 外文期刊>Infection and immunity >Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide
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Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide

机译：人类8型肺炎球菌荚膜多糖单克隆抗体对多形核细胞白细胞介素8分泌的调节。

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Pneumococcal capsular polysaccharide (PS) vaccines induce type-specific immunoglobulin M (IgM), IgG, and IgA. Type-specific IgG to the PS is sufficient to confer protection against the homologous serotype of the pneumococcus, but the efficacies of type-specific IgM and IgA are less well understood. We examined the in vitro activities and efficacies in mice of two human monoclonal antibodies (MAbs) to type 8 PS, NAD (IgA) and D11 (IgM). MAb-mediated opsonophagocytic killing was evaluated after coculture of type 8 pneumococci with human polymorphonuclear cells (PMNs), type-specific or control MAbs, and human complement sources. The effects of the MAbs on PMN interleukin-8 (IL-8) and IL-6 secretion were determined in supernatants from cocultures containing pneumococci and PMNs by enzyme-linked immunosorbent assay. MAb efficacy was determined in an intratracheal model of type 8 infection in mice with classical complement pathway deficiency. Both MAbs were protective in 100% of infected mice. Neither MAb promoted a significant amount of killing of type 8 pneumococci compared to its isotype control MAb. Both type-specific MAbs mediated complement-dependent modulation of PMN IL-8 secretion, with increased secretion at effector/target (E:T) ratios of 500:1 and 50:1 and reduced secretion at 1:5. Trypan blue staining revealed that PMNs cocultured with D11 were less viable at an E:T ratio of 1:5 than PMNs cocultured with the control MAb. PMN IL-6 secretion was increased by both type-specific and control MAbs. These results suggest that certain type-specific IgM and IgAs might contribute to host defense by modulation of the inflammatory response to pneumococci.
机译：肺炎球菌荚膜多糖（PS）疫苗诱导类型特异性免疫球蛋白M（IgM），IgG和IgA。 PS的类型特异性IgG足以对肺炎球菌的同源血清型提供保护，但是对类型特异性IgM和IgA的功效了解得还很少。我们检查了两种人类8型PS，NAD（IgA）和D11（IgM）单克隆抗体（MAb）的体外活性和功效。在将8型肺炎球菌与人多形核细胞（PMN），类型特异性或对照MAb以及人补体来源共培养后，评估了MAb介导的调理吞噬细胞的杀伤作用。通过酶联免疫吸附测定，在含有肺炎球菌和PMN的共培养物的上清液中，测定了单克隆抗体对PMN白介素8（IL-8）和IL-6分泌的影响。在具有经典补体途径缺陷的小鼠的气管内8型感染模型中确定MAb功效。两种单克隆抗体对100％的感染小鼠均具有保护作用。与同种型对照单抗相比，这两种单抗均未促进8型肺炎球菌的大量杀伤。两种类型特异性MAb介导PMN IL-8分泌的补体依赖性调节，效应子/靶标（E：T）比率为500：1和50：1的分泌增加，而1：5的分泌减少。台盼蓝染色显示与D11共培养的PMN在E：T比为1：5的情况下比与对照MAb共培养的PMN的生存能力差。特异性MAb和对照MAb均增加了PMN IL-6的分泌。这些结果表明，某些类型特异性的IgM和IgA可能通过调节对肺炎球菌的炎症反应来促进宿主防御。

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