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Normal levels of constitutive and death receptor-mediated apoptosis of peripheral blood neutrophils from patients with chronic idiopathic neutropenia.

机译:慢性特发性中性粒细胞减少症患者外周血中性粒细胞的组成型和死亡受体介导的凋亡水平正常。

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To investigate the role of neutrophil apoptosis in the pathogenesis of chronic neutropenia, we examined constitutive and death receptor-mediated apoptosis ex vivo of peripheral blood neutrophils obtained from six chronic idiopathic neutropenia (CIN) patients and six healthy adult blood donors. Apoptosis was quantified based on phosphatidylserine externalization and caspase-3 activation in freshly isolated neutrophils or after overnight cultivation of neutrophils in the absence or presence of pro- or anti-apoptotic factors, including the pan-caspase inhibitor, zVAD-fmk. Neutrophils from CIN patients receiving treatment with granulocyte colony-stimulating factor appeared to be more prone to constitutive apoptosis than cells from untreated patients; however, further investigations in larger cohorts of patients are needed to validate these pilot studies. Overall, the level of neutrophil apoptosis was similar in patient and control groups, thus supporting the notion that the underlying defect in these neutropenia patients lies elsewhere, such as in the bone marrow microenvironment.
机译:为了研究中性粒细胞凋亡在慢性中性粒细胞减少症发病机理中的作用,我们研究了从六名慢性特发性中性粒细胞减少症(CIN)患者和六名健康成人献血者获得的外周血中性粒细胞的本构和死亡受体介导的凋亡。在新鲜分离的中性粒细胞中,或在不存在或存在促凋亡或抗凋亡因子(包括泛半胱天冬酶抑制剂,zVAD-fmk)的中性粒细胞过夜培养后,基于磷脂酰丝氨酸外在化和caspase-3活化来量化凋亡。接受粒细胞集落刺激因子治疗的CIN患者的嗜中性粒细胞比未经治疗的患者的细胞更倾向于组成性凋亡。但是,需要对更大范围的患者进行进一步研究以验证这些先导研究。总体而言,患者和对照组的中性粒细胞凋亡水平相似,因此支持以下观点:这些中性粒细胞减少症患者的潜在缺陷位于其他地方,例如骨髓微环境。

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