Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milano, Italy.
Humanitas Clinical and Research Center, Rozzano, Italy; and.
J Leukoc Biol. 2014 May;95(5):817-825. doi: 10.1189/jlb.0913485. Epub 2013 Dec 30.
MVs are known vehicles of horizontal communication among cells, currently under scrutiny as powerful biomarkers in several pathological processes. The potential advantage of MVs relies on the assumption that their content reflects processes ongoing in pathologically relevant cell types. We have described that MVs of myeloid origin in the CSF are a marker of microglia/macrophage activation. Myeloid cells have different activation types, resulting in diverse functional phenotypes. Knowledge on the activation type of myeloid cells during disease would be of paramount importance for the understanding of ongoing pathogenic processes. We show here that macrophages activated in vitro in different ways all release increased amounts of MVs compared with NS cells. Moreover, we show that macrophage-derived MVs contain a repertoire of mRNAs that is not the result of casual sampling from the parental cells, as it is characterized by distinct mRNA enrichments and species. Nevertheless, mRNA content of MVs clearly allows identification in vivo of the activated phenotype of the cell of origin, indicating carryover of functional macrophage traits. We propose that detection of mRNAs in myeloid MVs permits identification of myeloid cell activation type during disease, allowing for further stratification of pathological processes.
MVs 是细胞间水平通讯的已知载体，目前正作为几种病理过程中的强大生物标志物受到关注。MVs 的潜在优势在于其内容反映了病理相关细胞类型中正在进行的过程。我们已经描述了脑脊液中髓系来源的 MVs 是小胶质细胞/巨噬细胞活化的标志物。髓系细胞有不同的激活类型，导致不同的功能表型。了解疾病期间髓系细胞的激活类型对于理解正在进行的致病过程至关重要。我们在这里表明，体外以不同方式激活的巨噬细胞释放的 MVs 量均高于 NS 细胞。此外，我们还表明，巨噬细胞衍生的 MVs 包含一组 mRNA，而不是源自亲本细胞的随机采样，因为其特征是独特的 mRNA 富集和种类。然而，MVs 的 mRNA 含量可明确鉴定出体内细胞起源的激活表型，表明功能巨噬细胞特征的传递。我们提出，在髓系 MVs 中检测到 mRNAs 可识别疾病期间髓系细胞的激活类型，从而进一步对病理过程进行分层。
