MACROPHAGE PHAGOCYTOSIS OF AGING NEUTROPHILS IN INFLAMMATION - PROGRAMMED CELL-DEATH IN THE NEUTROPHIL LEADS TO ITS RECOGNITION BY MACROPHAGES
MACROPHAGE PHAGOCYTOSIS OF AGING NEUTROPHILS IN INFLAMMATION - PROGRAMMED CELL-DEATH IN THE NEUTROPHIL LEADS TO ITS RECOGNITION BY MACROPHAGES
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DOI：
10.1172/jci113970
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发表时间：
1989-03-01
影响因子：
15.9
通讯作者：
HASLETT, C
中科院分区：
文献类型：
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作者：
SAVILL, JS;WYLLIE, AH;HASLETT, C
控制炎症的正常消退过程的机制知之甚少，但它们的阐明可能会导致对慢性炎症发病机制的更好理解。清除中性粒细胞及其潜在的组织毒性成分是解决问题的先决条件之一。吞噬的巨噬细胞是一个重要的处置途径，并在衰老的中性粒细胞的变化，与他们的识别巨噬细胞是本次调查的主题。培养24小时后，外周血或急性炎症关节中的人中性粒细胞比例增加，发生了程序性细胞死亡或凋亡的形态学变化。还证明了与时间相关的核小体间模式中的染色质切割，表明与程序性细胞死亡相关的内源性核酸内切酶活化。观察到中性粒细胞凋亡的增加特性和巨噬细胞对老龄中性粒细胞群体的识别程度之间存在密切的相关性，并且这些参数之间的直接关系在通过逆流离心分离成具有不同比例凋亡的组分的老龄中性粒细胞群体内得到证实。急性炎症关节的巨噬细胞优先摄取凋亡的中性粒细胞，并提出了原位过程发生的组织学证据。程序性细胞死亡是一种具有广泛生物学重要性的现象，以前在髓系细胞中没有描述过。因为它导致识别完整的衰老中性粒细胞，而这些中性粒细胞不一定排出它们的颗粒内容物，所以这些过程可能代表了在炎症期间去除中性粒细胞的机制，这也用于限制组织损伤的程度。
Mechanisms governing the normal resolution processes of inflammation are poorly understood, yet their elucidation may lead to a greater understanding of the pathogenesis of chronic inflammation. The removal of neutrophils and their potentially histotoxic contents is one prerequisite of resolution. Engulfment by macrophages is an important disposal route, and changes in the senescent neutrophil that are associated with their recognition by macrophages are the subject of this investigation. Over 24 h in culture an increasing proportion of human neutrophils from peripheral blood or acutely inflamed joints underwent morphological changes characteristic of programmed cell death or apoptosis. Time-related chromatin cleavage in an internucleosomal pattern indicative of the endogenous endonuclease activation associated with programmed cell death was also demonstrated. A close correlation was observed between the increasing properties of apoptosis in neutrophils and the degree of macrophage recognition of the aging neutrophil population, and a direct relationship between these parameters was confirmed within aged neutrophil populations separated by couterflow centrifugation into fractions with varying proportions of apoptosis. Macrophages from acutely inflamed joints preferentially ingested apoptotic neutrophils and histological evidence was presented for occurrence of the process in situ. Programmed cell death is a phenomenon of widespread biological importance and has not previously been described in a cell of the myeloid line. Because it leads to recognition of intact senescent neutrophils that have not necessarily disgorged their granule contents, these processes may represent a mechanism for the removal of neutrophils during inflammation that also serves to limit the degree of tissue injury.