Neutrophil survival is prolonged in the airways of healthy infants and infants with RSV bronchiolitis
Neutrophil survival is prolonged in the airways of healthy infants and infants with RSV bronchiolitis
复制标题
DOI：
10.1183/09031936.02.00278902
复制
发表时间：
2002-09-01
影响因子：
24.3
通讯作者：
Everard, ML
中科院分区：
文献类型：
--
作者：
Jones, A;Qui, JM;Everard, ML
感染呼吸道合胞病毒 (RSV) 的婴儿气道中的大量中性粒细胞被趋化因子（例如白细胞介素 8）招募，而特定的炎症分子可以延迟细胞凋亡，从而延长其寿命。本研究的目的是探讨RSV细支气管炎的气道分泌物是否含有影响中性粒细胞凋亡的因素。从24名RSV细支气管炎婴儿（31名婴儿对照和12名成人）中获取鼻灌洗液（NLF）。从健康成年志愿者中分离出的中性粒细胞与 NLF 在 Dulbecco 改良 Eagle 培养基 (DMEM) 中孵育 24 小时，并使用 Hoechst 33342 和碘化丙啶活力染料对细胞凋亡和坏死进行定量。使用白三烯-B-4、脂多糖和 IL-8 受体 CXCR2 抑制剂以及粒细胞-单核细胞集落刺激因子阻断抗体研究了延迟中性粒细胞凋亡的假定因素的存在。 NLF 的表征涉及热不稳定性、蛋白水解、脱氧核糖核酸酶消化和分子过滤的测试。来自患有 RSV 细支气管炎的婴儿和对照的 NLF 显着延迟了中性粒细胞凋亡，而来自健康成人的 NLF 则没有。这些抑制剂分子均未阻止这种细胞凋亡的延迟，但其活性对热敏感且>3 kDa。研究表明，婴儿鼻腔灌洗液可显着延迟中性粒细胞细胞凋亡。据推测，中性粒细胞在婴儿气道中的长期存活导致了患有呼吸道感染的婴儿气道中中性粒细胞的特征性积累。
Large numbers of neutrophils in the airway of infants infected by respiratory syncytial virus (RSV) are recruited by chemokines, such as interleukin-8, and specific inflammatory molecules can delay apoptosis increasing their longevity. The aim of this study was to investigate whether airway secretions in RSV bronchiolitis contain factors that influence neutrophil apoptosis.Nasal lavage fluid (NLF) was obtained from 24 infants with RSV bronchiolitis (31 infant controls and 12 adults). Neutrophils isolated from healthy adult volunteers were incubated with the NLF in Dulbecco modified Eagle medium (DMEM) for 24 h, and apoptosis and necrosis were quantified using Hoechst 33342 and propidium iodide viability dyes. The presence of putative factors that delay neutrophil apoptosis was investigated using inhibitors to leukotriene-B-4, lipopolysaccharide and the IL-8 receptor CXCR2, and blocking antibodies to granulocyte-monocyte colony-stimulating factor. Characterisation of NLF involved tests of thermal instability, proteolysis, deoxyribonuclease digestion and molecular filtration.NLF from infants with RSV bronchiolitis and controls significantly delayed neutrophil apoptosis, whereas NLF from healthy adults did not. None of these inhibitor molecules blocked this delay in apoptosis but activity was heat liable and >3 kDa.The study showed that nasal lavage fluid from infants significantly delays neutrophil apoptosis. The speculation is that the prolonged survival of neutrophils in the infant airway contributes to the characteristic accumulation of neutrophils in the airways of infants with respiratory infections.