Improved stimulation of human dendritic cells by receptor engagement with surface-modified microparticles
Improved stimulation of human dendritic cells by receptor engagement with surface-modified microparticles
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DOI：
10.1080/1061186031000072978
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发表时间：
2003-01-01
影响因子：
4.5
通讯作者：
Walter, E
中科院分区：
文献类型：
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作者：
Kempf, M;Mandal, B;Walter, E
树突状细胞(DC)需要被刺激才能启动免疫反应。这项研究调查了携带DC表达的特定受体特异性抗体的微粒是否可以诱导对这些细胞的刺激。将普通微粒与表面负载了人CD40、FcGamma、αvbeta3和αvbeta5整合素受体特异性抗体的微粒进行了比较。抗体被物理吸附或共价连接到微粒表面。抗CD40抗体和人免疫球蛋白被固定在微粒表面，诱导DC成熟和活化，CD83和CD86表达上调。IL-12的分泌水平可检测到，但相对较低。两种抗整合素抗体(抗αvbeta3和抗alphavbeta5)均可诱导DC显著成熟，但只有抗alphavbeta3抗体可显著激活DC，而抗alphavbeta5抗体不能显著激活DC。使用带有共价连接抗体的微粒时，刺激作用最明显，但当抗体物理吸附到聚苯乙烯和可生物降解的聚丙交酯-乙交酯微粒上时，也观察到较小程度的刺激作用。通过特定配体的表面偶联来改造微粒以刺激树突状细胞，可能会增加微粒疫苗递送系统的有效性。
Dendritic cells (DC) need to be stimulated before they can function to initiate immune responses. This study investigates whether microparticles loaded with antibodies specific for selected receptors expressed by DC can induce stimulation of these cells. Plain microparticles were compared with microparticles which were surface-loaded with specific antibodies for human CD40, Fcgamma, alphavbeta3 and alphavbeta5 integrin receptors. The antibodies were either physically adsorbed or covalently linked to the microparticle surface. Anti-CD40 antibody and human IgG immobilised on the surface of microparticles induced enhanced DC maturation and activation as expressed by CD83 and CD86 upregulation. IL-12 secretion was induced at a detectable but relatively low level. Both anti-integrin antibodies (anti-alphavbeta3 and anti-alphavbeta5) induced comparable and considerable maturation of DC, but only anti-alphavbeta3 antibody induced significant activation of DC, whereas anti-alphavbeta5 did not. The stimulatory effects were most pronounced by employing microparticles with covalently linked antibodies, but were also observed to a minor extent when the antibodies were physically adsorbed to polystyrene and biodegradable poly(lactide-co-glycolide) microparticles. Engineering of microparticles by surface conjugation of specific ligands to stimulate DC may increase the effectiveness of microparticulate vaccine delivery systems.