Kendall Mark, Mitchell Thomas J, Costigan George, Armitage Mark, Lenzo Jason C, Thomas Jennifer A, von Garnier Christophe, Zosky Graeme R, Turner Debra J, Stumbles Phil A, Sly Peter D, Holt Patrick G, Thomas Wayne R
The PowderJect Centre for Gene and Drug Delivery Research, University of Oxford, UK.
J Allergy Clin Immunol. 2006 Feb;117(2):275-82. doi: 10.1016/j.jaci.2005.09.049. Epub 2005 Dec 2.
Biolistic injections provide a needle-free delivery of antigen-laden microparticles to the epithelium. The precision of the injection preferentially targets the Langerhans cell network, which, although ideal for vaccination, might not be suitable for the downregulation of immune responses in immunotherapy.
We sought to determine the ability of biolistic injection of antigen into the epithelium of sensitized mice to inhibit IgE antibody and lung inflammatory responses produced by further exposure to antigen.
Mice were sensitized by means of a needle injection of ovalbumin (OVA) in alum and given a series of biolistic injections of OVA or vehicle control, followed by a boost of OVA in alum. Serum IgE and IgG antibodies were measured before and after the boost. The mice were then challenged intranasally, and the infiltration of inflammatory cells was measured by means of bronchoalveolar lavage. Airway reactivity of the challenged mice was measured by examining responses to methacholine with forced oscillatory techniques.
Biolistic injection of OVA into the dorsal skin of sensitized mice markedly inhibited IgE and IgG1 antibody responses induced by boosting. IgG2a antibody responses were reduced rather than stimulated. The eosinophilic inflammation in the bronchoalveolar lavage fluid induced by intranasal challenge was also markedly inhibited. Lung hyperreactivity showed an initial increase and then a decrease of responsiveness to methacholine, with elastance returning to the level of unsensitized mice. Biolistic injection into the buccal epithelium was also inhibitory.
Biolistic injection of allergen inhibited the boosting of IgE antibody and eosinophilic lung inflammatory responses without inducing T(H)1 immunity.
生物弹道注射可将载有抗原的微粒无针递送至上皮组织。注射的精准度优先靶向朗格汉斯细胞网络，该网络虽对疫苗接种十分理想，但可能不适用于免疫治疗中免疫反应的下调。
我们试图确定向致敏小鼠的上皮组织进行生物弹道注射抗原抑制再次接触抗原所产生的IgE抗体和肺部炎症反应的能力。
通过在明矾中用针注射卵清蛋白（OVA）使小鼠致敏，并对其进行一系列OVA或赋形剂对照的生物弹道注射，随后在明矾中加强注射OVA。在加强注射前后测量血清IgE和IgG抗体。然后对小鼠进行鼻内激发，并通过支气管肺泡灌洗测量炎症细胞浸润情况。通过强迫振荡技术检测对乙酰甲胆碱的反应来测量激发后小鼠的气道反应性。
向致敏小鼠的背部皮肤进行生物弹道注射OVA可显著抑制加强注射诱导的IgE和IgG1抗体反应。IgG2a抗体反应减弱而非增强。鼻内激发诱导的支气管肺泡灌洗液中的嗜酸性粒细胞炎症也受到显著抑制。肺高反应性表现为对乙酰甲胆碱的反应性先增加后降低，弹性恢复到未致敏小鼠的水平。向颊上皮进行生物弹道注射也具有抑制作用。
生物弹道注射变应原可抑制IgE抗体的加强反应和嗜酸性粒细胞肺部炎症反应，而不诱导Th1免疫。
