Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses
Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses
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DOI：
10.1182/blood-2004-01-0207
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发表时间：
2004-08-15
期刊：
影响因子：
20.3
通讯作者：
Rath, S
中科院分区：
文献类型：
--
作者：
Mangla, A;Khare, A;Rath, S
布鲁顿酪氨酸激酶（Btk）是Tec家族的一种非受体相关酪氨酸激酶，似乎参与许多骨髓细胞功能。我们发现，缺乏功能性Btk的X-连锁免疫缺陷（XID）小鼠的巨噬细胞不能产生有效的活性氧中间体（ROI）爆发。在XID巨噬细胞中，炎性刺激诱导的凋亡性细胞死亡也增强。细菌颗粒的吞噬作用在它们中仅受到轻微影响。在体内，XID小鼠在实验性自身免疫性脑脊髓炎（EAE）、葡聚糖硫酸钠（DSS）诱导的结肠炎和角叉菜胶诱导的急性水肿模型中表现出炎症性疾病的严重程度降低。此外，XID小鼠中的多形嗜中性粒细胞（PMN）显示出不良的ROI和一氧化氮（NO）诱导，沿着PMN向腹膜炎症的募集减少。XID小鼠显示外周血中的PMN数量减少，并且它们的骨髓显示单核细胞和粒细胞谱系的数量减少，延伸到最早的祖细胞群体。因此，Btk可能在骨髓谱系的发育和功能过程中的多个点发挥重要作用，影响体内许多感染性和非感染性炎症事件的结果。(C)2004年，美国血液学会。
Bruton tyrosine kinase (Btk), a nonreceptor-associated tyrosine kinase of the Tec family, appears to participate in many myeloid cell functions. We show that macrophages from X-linked immunodeficient (XID) mice lacking functional Btk cannot generate efficient bursts of reactive oxygen intermediates (ROIs). The induction of apoptotic cell death by inflammatory stimuli is also enhanced in XID macrophages. Phagocytosis of bacterial particles is only marginally affected in them. In vivo, XID mice show reduced severity of inflammatory diseases in models of experimental autoimmune encephalomyelitis (EAE), dextran sulfate sodium (DSS)-induced colitis, and carrageenan-induced acute edema. Also, polymorphonuclear neutrophil granulocytes (PMNs) in XID mice show poor ROI and nitric oxide (NO) induction, along with a reduction in PMN recruitment to peritoneal inflammation. XID mice show reduction in PMN numbers in peripheral blood, and their bone marrow shows a reduction in the numbers of both monocytic and granulocytic lineages, extending to the earliest progenitor populations. Thus, Btk is likely to play a significant role at multiple points during the development and functioning of the myeloid lineages, affecting the outcome of many infectious as well as noninfectious inflammatory events in vivo. (C) 2004 by The American Society of Hematology.