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Adjuvant effects of liposomes containing lipid A: enhancement of liposomal antigen presentation and recruitment of macrophages.

机译:含脂质A的脂质体的佐剂作用:增强脂质体抗原呈递和巨噬细胞募集。

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Liposomes containing lipid A induced potent humoral immune responses in mice against an encapsulated malaria antigen (R32NS1) containing NANP epitopes. The immune response was not enhanced by lipid A alone or by empty liposomes containing lipid A. Experiments to investigate the adjuvant mechanisms of liposomes and lipid A revealed that liposome-encapsulated R32NS1 was actively presented by bone marrow-derived macrophages to NANP-specific cloned T cells. The degree of presentation was related to the amount of liposomal antigen added per macrophage in the culture medium. At high cell densities, poor presentation occurred when liposomes lacked lipid A but excellent presentation occurred when the liposomes contained lipid A. Liposomes containing lipid A and encapsulated antigen also activated gamma interferon-treated macrophages to produce nitric oxide. Macrophage activation and antigen presentation occurred with liposomes that could not be detected by the Limulus amebocyte lysis assay. Intraperitoneal injection of liposomal lipid A caused a marked increase in the recruitment of immature (peroxidase-positive) macrophages to the peritoneum. On the basis of these experiments, we propose that the mechanism of the adjuvant action of liposomal lipid A is partly due to increased antigen presentation by macrophages and partly due to recruitment of an increased number of macrophages serving as antigen-presenting cells.
机译:包含脂质A的脂质体在小鼠中诱导了针对包含NANP表位的封装疟疾抗原(R32NS1)的有效体液免疫反应。单独的脂质A或含有脂质A的空脂质体均未增强免疫反应。研究脂质体和脂质A佐剂机制的实验表明,脂质体包裹的R32NS1是由骨髓巨噬细胞主动呈递给NANP特异性克隆的T的。细胞。呈递的程度与培养基中每个巨噬细胞添加的脂质体抗原的量有关。在高细胞密度下,当脂质体缺乏脂质A时,显示效果较差,而当脂质体包含脂质A时,显示效果则良好。含有脂质A和包封抗原的脂质体也会活化经γ-干扰素处理的巨噬细胞,从而产生一氧化氮。巨噬细胞的活化和抗原呈递发生在脂质体上,而脂质体的am细胞溶解分析无法检测到。腹膜内注射脂质体脂质A导致未成熟(过氧化物酶阳性)巨噬细胞向腹膜的募集明显增加。基于这些实验,我们提出脂质体脂质A的佐剂作用机制部分是由于巨噬细胞增加的抗原呈递,部分是由于募集了更多数目的用作抗原呈递细胞的巨噬细胞。

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