Eyles J E, Bramwell V W, Williamson E D, Alpar H O
DERA (Chemical and Biological Defence Sector), Porton Down, Wiltshire SP4 OJQ, Salisbury, UK.
Vaccine. 2001 Sep 14;19(32):4732-42. doi: 10.1016/s0264-410x(01)00220-1.
With a view to developing improved mucosal immunisation strategies, we have quantitatively investigated the uptake of fluorescent polystyrene carboxylate microspheres (1.1 microm diameter), using histology and fluorescence-activated cell sorting, following intranasal delivery to BALB/c mice. To qualify these biodistribution data, antigen specific memory and effector responses in the spleens of mice immunised nasally with Yersinia pestis V antigen loaded poly(lactide) (PLA) microspheres (1.5 microm diameter) were assessed at 4, 7 and 11 days. Irrespective of administration vehicle volume (10 or 50 microl), appreciable numbers of fluorescent microspheres were detected within nasal associated lymphoid tissues (NALT) and draining cervical lymph nodes. Nasal administration of the particles suspended in 50 microl volumes of phosphate-buffered saline (PBS) served to deposit the fluorescent microspheres throughout the respiratory tract (P<0.05). In these animals, appreciable particle uptake into the mediastinal lymph node was noted (P<0.05). Also, spleens removed from mice 10 days after fluorescent particle application contained significantly more microspheres if the suspension had been nasally instilled using a 50 microl volume (P<0.05). Appreciable memory (and effector from day 7) responses were detected in mediastinal lymph nodes removed from mice immunised nasally with 50 microl volumes of microparticulated or soluble V antigen. Immunological responses in splenic tissue removed 7 days after intranasal immunisation corroborated the thesis that the spleen can act as an inductive site following bronchopulmonary deposition of particulated antigen: upon exposure to V in vitro, splenic T-cells from mice nasally immunised with 50 microl volumes of microspheres incorporated statistically greater (P<0.05) quantities of [3H]thymidine into newly synthesised DNA than did T-cells from cohorts nasally immunised with 50 microl volumes of V in solution. Similarly, significant numbers of anti-V IgG secreting cells were only detected in spleens from mice immunised intramuscularly or nasally with microparticles. These immunological and biodistribution data support the tenet that, following an appropriate method of mucosal delivery, microparticles can translocate to tissues in the systemic compartment of the immune system and thence provoke immunological reactions therein.
为了开发改进的黏膜免疫策略，我们采用组织学和荧光激活细胞分选技术，对直径1.1微米的荧光聚苯乙烯羧酸盐微球经鼻内给药至BALB/c小鼠后的摄取情况进行了定量研究。为了验证这些生物分布数据，在第4、7和11天评估了用鼠疫耶尔森菌V抗原负载的聚丙交酯（PLA）微球（直径1.5微米）经鼻免疫的小鼠脾脏中的抗原特异性记忆和效应反应。无论给药载体体积（10或50微升）如何，在鼻相关淋巴组织（NALT）和引流颈淋巴结中均检测到大量荧光微球。经鼻给予悬浮于50微升磷酸盐缓冲盐水（PBS）中的颗粒，可使荧光微球沉积于整个呼吸道（P<0.05）。在这些动物中，观察到有相当数量的颗粒摄取进入纵隔淋巴结（P<0.05）。此外，如果使用50微升体积经鼻滴注悬浮液，在荧光颗粒给药10天后从小鼠体内取出的脾脏中含有明显更多的微球（P<0.05）。在用50微升体积的微粒化或可溶性V抗原经鼻免疫的小鼠取出的纵隔淋巴结中检测到明显的记忆（以及从第7天开始的效应）反应。经鼻免疫7天后取出的脾脏组织中的免疫反应证实了这样的论点，即脾脏可作为颗粒性抗原经支气管肺沉积后的诱导部位：在体外接触V后，经鼻用50微升体积微球免疫的小鼠脾脏T细胞比经鼻用50微升体积溶液中的V免疫的同组小鼠的T细胞，将统计学上更多（P<0.05）的[3H]胸腺嘧啶掺入新合成的DNA中。同样，仅在经肌肉注射或经鼻用微粒免疫的小鼠脾脏中检测到大量分泌抗V IgG的细胞。这些免疫和生物分布数据支持这样的原则，即采用适当的黏膜给药方法后，微粒可转移至免疫系统全身 compartment的组织中，并在其中引发免疫反应。
原文中“systemic compartment”表述不太准确，可能是“systemic compartment of the immune system”（免疫系统的全身部分），翻译时尽量贴近原文进行了翻译。
