Changes in apoptosis of human polymorphonuclear granulocytes with aging
Changes in apoptosis of human polymorphonuclear granulocytes with aging
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DOI：
10.1016/s0047-6374(96)01881-7
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发表时间：
1997-06-01
影响因子：
5.3
通讯作者：
Dupuis, G
中科院分区：
文献类型：
--
作者：
Fulop, T;Fouquet, C;Dupuis, G
随着年龄的增长，免疫系统中的细胞和器官水平发生了许多变化，最终导致免疫反应下降。我们的目的是在目前的工作是研究细胞凋亡的多形核粒细胞（PMN）与老化的各种刺激下，因为细胞凋亡可能发挥重要作用，在一些病理遇到老化。健康年轻人（20-25岁）和老年人（65-85岁）受试者的中性粒细胞（PMN）在无菌培养24小时后进行了检查。刺激剂包括：佛波醇肉豆蔻酸乙酸酯（PMA）、过氧化氢（H2 O2）、N-甲酰基-甲硫氨酰基-亮氨酰基苯丙氨酸（FMLP）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、还原型谷胱甘肽（GSH）、脂多糖（LPS）和白细胞介素2（IL-2）。通过传统的平板染色、流式细胞术染色和DNA凝胶电泳评估细胞凋亡。结果发现，在没有刺激的情况下，PMN对凋亡的敏感性随着年龄的增长而略有增加。在PMA、H_2O_2等多种刺激下，PMN凋亡率几乎为100%，而FMLP、oxLDL和GSH处理对PMN凋亡率无明显影响。在GM-CSF、IL-2和LPS刺激下，观察到细胞凋亡程度的显著年龄相关变化。这些药物能够显着防止年轻受试者的中性粒细胞凋亡，而只有GM-CSF能够轻微调节它在老年受试者的中性粒细胞。从这些结果中，我们认为，随着年龄的增长，中性粒细胞凋亡的变化可能在某些免疫系统相关的衰老病理学，如癌症，感染和自身免疫性疾病的发病率增加中发挥作用。(C)1997 Elsevier Science爱尔兰有限公司
Many alterations with aging occur at the cellular and organic levels in the immune system ultimately leading to a decrease in the immune response. Our aim in the present work was to study apoptosis of polymorphonuclear granulocytes (PMN) with aging under various stimulations since apoptosis might play an important role in several pathologies encountered with aging. The PMN of healthy young (20-25 years) and elderly (65-85 years) subjects were examined after 24 h of sterile culture with and without stimulation. The stimulating agents included: phorbol myristate acetate (PMA), hydrogen peroxide (H2O2), N-formyl-methionyl-leucyl phenylalanine (FMLP), granulocyte-macrophage colony stimulating factor (GM-CSF), reduced glutathione (GSH), lipopolysaccharide (LPS) and interleukin 2 (IL-2). Apoptosis was assessed by traditional staining of the plates, by flow cytometric staining and DNA gel electrophoresis. It was found that without stimulation the susceptibility of PMN to apoptosis was slightly increased with aging. Under various stimulations, such as PMA, H2O2, apoptosis was almost 100%, while the treatment by FMLP, oxLDL and GSH did not change its extent in PMN obtained either from young or elderly subjects. Marked age-related changes were observed in the extent of apoptosis under stimulation with GM-CSF, IL-2 and LPS. These agents were able to significantly prevent apoptosis in PMN of young subjects, while only the GM-CSF was able to slightly modulate it in neutrophils of elderly subjects. From these results, we suggest that changes in apoptosis of PMN with aging could play a role in the increased incidence of certain immune system related pathologies of aging, such as cancer, infections and autoimmune disorders. (C) 1997 Elsevier Science Ireland Ltd.