Fernández Gabriela C, Ramos María V, Gómez Sonia A, Dran Graciela I, Exeni Ramón, Alduncín Marta, Grimoldi Irene, Vallejo Graciela, Elías-Costa Christian, Isturiz Martín A, Palermo Marina S
Division of Immunology of the Institute of Hematological Investigations, Academia Nacional de Medicina, Buenos Aires, Argentina.
J Leukoc Biol. 2005 Oct;78(4):853-61. doi: 10.1189/jlb.0505251. Epub 2005 Jul 26.
Monocytes (Mo) mediate central functions in inflammation and immunity. Different subpopulations of Mo with distinct phenotype and functional properties have been described. Here, we investigate the phenotype and function of peripheral Mo from children with hemolytic uremic syndrome (HUS). For this purpose, blood samples from patients in the acute period of HUS (HUS AP) were obtained on admission before dialysis and/or transfusion. The Mo phenotypic characterization was performed on whole blood by flow cytometry, and markers associated to biological functions were selected: CD14 accounting for lipopolysaccharide (LPS) responsiveness, CD11b for adhesion, Fc receptor for immunoglobulin G type I (FcgammaRI)/CD64 for phagocytosis and cytotoxicity, and human leukocyte antigen (HLA)-DR for antigen presentation. Some of these functions were also determined. Moreover, the percentage of CD14+ CD16+ Mo was evaluated. We found that the entire HUS AP Mo population exhibited reduced CD14, CD64, and CD11b expression and decreased LPS-induced tumor necrosis factor production and Fcgamma-dependent cytotoxicity. HUS AP showed an increased percentage of CD14+ CD16+ Mo with higher CD16 and lower CD14 levels compared with the same subset from healthy children. Moreover, the CD14++ CD16- Mo subpopulation of HUS AP had a decreased HLA-DR expression, which correlated with severity. In conclusion, the Mo population from HUS AP patients presents phenotypic and functional alterations. The contribution to the pathogenesis and the possible scenarios that led to these changes are discussed.
单核细胞（Mo）在炎症和免疫中发挥核心作用。已描述了具有不同表型和功能特性的Mo不同亚群。在此，我们研究溶血尿毒综合征（HUS）患儿外周血Mo的表型和功能。为此，在透析和/或输血前入院时采集HUS急性期（HUS AP）患者的血样。通过流式细胞术对全血进行Mo表型特征分析，并选择与生物学功能相关的标志物：CD14代表对脂多糖（LPS）的反应性，CD11b代表黏附，免疫球蛋白G I型Fc受体（FcγRI）/CD64代表吞噬作用和细胞毒性，以及人类白细胞抗原（HLA）-DR代表抗原呈递。还测定了其中一些功能。此外，评估了CD14+ CD16+ Mo的百分比。我们发现，整个HUS AP Mo群体表现出CD14、CD64和CD11b表达降低，LPS诱导的肿瘤坏死因子产生和Fcγ依赖性细胞毒性降低。与健康儿童的同一亚群相比，HUS AP显示CD14+ CD16+ Mo百分比增加，CD16水平较高而CD14水平较低。此外，HUS AP的CD14++ CD16- Mo亚群HLA-DR表达降低，这与疾病严重程度相关。总之，HUS AP患者的Mo群体存在表型和功能改变。讨论了其对发病机制的贡献以及导致这些变化的可能情况。
