Abstract:
Sickle cell disease (SCD) is marked by episodic vaso-occlusive crisis (VOC). Recurrent VOC creates a pro-inflammatory state that induces phenotypic alterations in innate immune cells. Monocytes are of particular interest to VOC pathophysiology because they are especially malleable to inflammatory signaling. Indeed, inflammatory disease states such as chronic obstructive pulmonary disease (COPD), obesity and atherosclerosis are known to influence monocyte development and alter monocyte subpopulations. In this study, we describe SCD monocyte subsets by performing immunophenotypic flow cytometric, enzymatic, and morphologic analysis on peripheral blood. Herein, we add to the growing body of evidence suggesting aberrant monocyte populations underpin VOC pathophysiology. We found that SCD monocytes possess an immature phenotype as demonstrated by 1) decreased CD4 positivity (p < .01), 2) low α-naphthyl butyrate esterase (ANBE) expression, and 3) naïve morphologic features. We additionally found an increase in CD14+CD16-CD4- monocytes (p < .01), a subset associated with the impaired immune response of post-trauma patients. Interestingly, we also found a large proportion of CD14+CD4-HLA-DR- monocytes which, under normal circumstances, are exclusively found in neonates (p < .01). Finally, we report an increase in nonclassical monocytes (CD14dimCD16+), a subset recently shown to have a critical role in prevention and recovery from VOC.
摘要:
镰状细胞病(SCD)的特征是偶发性血管闭塞性危象(VOC)。复发的VOC产生诱导先天免疫细胞表型改变的促炎状态。单核细胞对VOC病理生理学特别感兴趣,因为它们对炎症信号传导特别有延展性。的确,炎症性疾病状态,如慢性阻塞性肺疾病(COPD),已知肥胖和动脉粥样硬化会影响单核细胞发育并改变单核细胞亚群。在这项研究中,我们通过进行免疫表型流式细胞术描述SCD单核细胞亚群,酶,和外周血的形态学分析。在这里,我们增加了越来越多的证据,表明异常单核细胞群支持VOC病理生理学。我们发现SCD单核细胞具有未成熟的表型,如1)CD4阳性降低(p<0.01),2)低α-萘基丁酸酯酶(ANBE)表达,和3)幼稚的形态学特征。我们还发现CD14+CD16-CD4-单核细胞增加(p<0.01),与创伤后患者免疫反应受损相关的子集。有趣的是,我们还发现了很大比例的CD14+CD4-HLA-DR-单核细胞,在正常情况下,仅在新生儿中发现(p<0.01)。最后,我们报告了非经典单核细胞(CD14dimCD16+)的增加,一个最近显示在预防和恢复VOC中起关键作用的子集。