Centro di Ricerca Interdipartimentale per le Biotecnologie Innovative, Padova, Italy.
J Innate Immun. 2011;3(6):614-22. doi: 10.1159/000327839. Epub 2011 Jun 16.
We show that apidaecin binds to human macrophages, monocytes and dendritic cells, displaying different intracellular distributions and inducing diversified effects. An apidaecin-cell association was detectable at concentrations as low as 5 μM and increased without saturation until 60 μM, was receptor independent and required a physiological temperature (37°C). For apidaecin, cytosolic localization was prevalent in macrophages and endosomal localization in monocytes, and associations with the plasma membrane were predominant in dendritic cells. Apidaecin upregulated T-lymphocyte co-stimulatory molecule CD80 and cytokine/chemokine production in macrophages, but not in monocytes and dendritic cells. Suboptimal stimulatory doses (5-10 μM) of apidaecin partially inhibited the lipopolysaccharide (LPS)-induced increase in major histocompatibility complex class II (MHCII) and CD86 in macrophages, and the release of selected cytokines/chemokines by both macrophages [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] and monocytes [IL-6, TNF-α, basic fibroblast growth factor (FGF) and eotaxin]. Apidaecin had a double-edged effect: at low concentrations it partially antagonized LPS-stimulatory effects on both macrophages and monocytes while it stimulated pro-inflammatory and pro-immune functions of macrophages at higher concentrations.
我们证明，蜂肽与人巨噬细胞、单核细胞和树突状细胞结合，显示出不同的细胞内分布，并诱导多样化的效应。在低至 5 μM 的浓度下即可检测到蜂肽-细胞的关联，并且这种关联增加而不会饱和，直到 60 μM，这种关联不依赖于受体，并且需要生理温度（37°C）。对于蜂肽，在巨噬细胞中主要是细胞质定位，在单核细胞中主要是内体定位，而在树突状细胞中主要是与质膜的关联。蜂肽在上调 T 淋巴细胞共刺激分子 CD80 和细胞因子/趋化因子的产生方面，在巨噬细胞中表现明显，但在单核细胞和树突状细胞中则不然。蜂肽的亚最佳刺激剂量（5-10 μM）部分抑制了脂多糖（LPS）诱导的巨噬细胞主要组织相容性复合体 II（MHCII）和 CD86 的增加，以及巨噬细胞[白细胞介素（IL）-6 和肿瘤坏死因子（TNF）-α]和单核细胞[IL-6、TNF-α、碱性成纤维细胞生长因子（FGF）和嗜酸性粒细胞趋化因子]释放选定的细胞因子/趋化因子。蜂肽具有双重作用：在低浓度时，它部分拮抗 LPS 对巨噬细胞和单核细胞的刺激作用，而在较高浓度时则刺激巨噬细胞的促炎和免疫功能。
