Tabata Y, Inoue Y, Ikada Y
Research Center for Biomedical Engineering, Kyoto University, Japan.
Vaccine. 1996 Dec;14(17-18):1677-85. doi: 10.1016/s0264-410x(96)00149-1.
Induction of systemic and mucosal immune responses following oral administration of biodegradable poly(D,L-lactic acid) (PDLLA) microspheres containing a model antigen, ovalbunin (OVA) was studied using microspheres with different average diameters of 0.6, 1.0, 4.0, 7.0, 11.0, 15.0, 21.0, and 26.0 microns. They were prepared from double emulsion with the solvent evaporation method, followed by size fractionation on counterflow elutriation. OVA was released from the microspheres in vitro over 80 days, irrespective of their size. Production of the serum anti-OVA IgG antibody and secretory OVA-specific IgA antibody in the mice gut was assessed following the oral administration of PDLLA microspheres containing OVA. Microspheres with a diameter of 4.0 microns enhanced the serum antibody in contrast with that of free OVA, but were not effective in inducing the gut secretion of IgA antibody. On the other hand, OVA-containing microspheres with a diameter of 7.0 microns enhanced IgA secretion to a significant extent compared with free OVA, whereas those with 26.0 microns in diameter were ineffective. Body distribution study revealed that the amount of microspheres taken up into Peyer's patches (PP) increased with the increasing size up to 11.0 microns, thereafter decreased, and finally became zero when their diameters were 21.0 microns or larger. The microspheres taken up into PP were translocated to the spleen, but no microspheres were noticed in the spleen when the size was larger than 5 microns. After being taken up inot PP, microspheres < 5 microns in diameter seemed to be transported to the spleen, a systemic lymphoid tissue, where the released antigen stimulated a serum antibody response, but larger microspheres probably remained at PP without being translocated to the spleen over the course of their antigen release, leading to induction of IgA secretion. It was concluded that the body distribution pattern of microspheres following the PP uptake was a key factor to regulate the induction of systemic and mucosal immune responses.
使用平均直径分别为0.6、1.0、4.0、7.0、11.0、15.0、21.0和26.0微米的微球，研究了口服含有模型抗原卵清蛋白（OVA）的可生物降解聚（D，L-乳酸）（PDLLA）微球后全身和黏膜免疫反应的诱导情况。它们通过溶剂蒸发法从复乳体制备，随后通过逆流淘析进行尺寸分级。无论微球大小如何，OVA在体外80天内均从微球中释放。在口服含有OVA的PDLLA微球后，评估小鼠肠道中血清抗OVA IgG抗体和分泌型OVA特异性IgA抗体的产生。与游离OVA相比，直径为4.0微米的微球增强了血清抗体，但在诱导肠道IgA抗体分泌方面无效。另一方面，直径为7.0微米的含OVA微球与游离OVA相比，显著增强了IgA分泌，而直径为26.0微米的微球则无效。体内分布研究表明，进入派尔集合淋巴结（PP）的微球数量随着尺寸增加至11.0微米而增加，此后减少，当直径为21.0微米或更大时最终变为零。进入PP的微球转移至脾脏，但当尺寸大于5微米时，脾脏中未发现微球。直径<5微米的微球被PP摄取后似乎被转运至脾脏，即全身淋巴组织，释放的抗原在此刺激血清抗体反应，但较大的微球可能在其抗原释放过程中留在PP处而未转移至脾脏，从而导致IgA分泌的诱导。得出的结论是，PP摄取后微球的体内分布模式是调节全身和黏膜免疫反应诱导的关键因素。
