Glucocorticoids inhibit apoptosis of human neutrophils.
Glucocorticoids inhibit apoptosis of human neutrophils.
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DOI：
10.1182/blood.v86.8.3181.bloodjournal8683181
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发表时间：
1995-10
期刊：
影响因子：
20.3
通讯作者：
W. Liles;D. Dale;S. Klebanoff
中科院分区：
文献类型：
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作者：
W. Liles;D. Dale;S. Klebanoff
人类中性粒细胞迅速发生细胞凋亡。由于已知糖皮质激素可调节一系列中性粒细胞功能活动并诱导易感淋巴细胞群体快速凋亡，因此我们研究了糖皮质激素对成熟人中性粒细胞凋亡的影响。在体外维持的中性粒细胞培养物中，在 12、24 和 48 小时进行评估时，糖皮质激素、地塞米松、6α-甲基泼尼松龙和氢化可的松可抑制细胞凋亡形态的发展 59% 至 90%。相反，缺乏抗炎活性的皮质类固醇和黄体酮未能影响细胞凋亡形态特征的发展。 24小时时使细胞凋亡减少50%所需的地塞米松浓度约为5×10~(-8)mol/L，这是地塞米松治疗后血浆中可达到的浓度。在此期间，地塞米松（10(-6) mol/L）（而非黄体酮）使亚二倍体（凋亡）细胞核的百分比降低了 40% 至 90%。同样，地塞米松减少了与细胞凋亡相关的 DNA 裂解，并延长了培养物中中性粒细胞的活力 12 至 48 小时。与粒细胞集落刺激因子 (100 ng/mL) 的作用相比，糖皮质激素介导的中性粒细胞凋亡调节在性质上相似，但幅度较小。因此，糖皮质激素通过延迟细胞凋亡对人类中性粒细胞的存活发挥保护作用。
Human neutrophils rapidly undergo apoptotic cell death. Because glucocorticoids are known to modulate an array of neutrophil functional activities as well as induce rapid apoptosis in susceptible lymphocyte populations, we have examined the effects of glucocorticoids on apoptosis in mature human neutrophils. In cultures of neutrophils maintained in vitro, the glucocorticoids, dexamethasone, 6 alpha-methylprednisolone, and hydrocortisone, inhibited the development of apoptotic morphology by 59% to 90% when assessed at 12, 24, and 48 hours. In contrast, corticosteroids lacking anti-inflammatory activity and progesterone failed to affect development of the morphologic features of apoptosis. The concentration of dexamethasone required to reduce apoptosis by 50% at 24 hours was approximately 5 x 10(-8) mol/L, a concentration that is achievable in plasma after dexamethasone treatment. Dexamethasone (10(-6) mol/L), but not progesterone, reduced the percentage of hypodiploid (apoptotic) nuclei by 40% to 90% over this time course. Similarly, dexamethasone reduced the DNA cleavage associated with apoptosis and prolonged the viability of neutrophils maintained in culture for 12 to 48 hours. Glucocorticoid-mediated modulation of neutrophil apoptosis was qualitatively similar, but lesser in magnitude, when compared with the effects of granulocyte colony-stimulating factor (100 ng/mL). Thus, glucocorticoids exert a protective effect on human neutrophil survival by delaying apoptosis.