Fusion of azurophil granules with phagosomes and activation of the tyrosine kinase Hck are specifically inhibited during phagocytosis of mycobacteria by human neutrophils.
Fusion of azurophil granules with phagosomes and activation of the tyrosine kinase Hck are specifically inhibited during phagocytosis of mycobacteria by human neutrophils.
复制标题
在人类中性粒细胞吞噬分枝杆菌的过程中，天青颗粒与吞噬体的融合以及酪氨酸激酶 Hck 的激活受到特异性抑制。
作者：
Elsa;Xavier Darzacq;C. Astarie;Mamadou Daffé;Jero Calafat;I. Maridonneau
病原性分枝杆菌寄生于巨噬细胞内，并存在于不与溶酶体颗粒融合的吞噬体内。分枝杆菌也被嗜中性粒细胞内化，嗜中性粒细胞具有至少两种类型的颗粒，特异性颗粒和嗜天青颗粒，后者是特化的溶酶体。在这里，我们研究了分枝杆菌的能力，以抑制这些颗粒与他们的吞噬体在人类中性粒细胞的融合。结果发现，当致病性（堪萨斯分枝杆菌和鸟分枝杆菌）或非致病性（耻垢分枝杆菌和草分枝杆菌）分枝杆菌被中性粒细胞内化，他们诱导抑制嗜天青颗粒融合吞噬体，即使当他们血清调理。与此相反，特定颗粒内容物的分泌和O2-的产生，这两者都有助于中性粒细胞杀菌反应，被触发。Hck是与嗜天青颗粒相关的Src家族酪氨酸激酶。在酵母聚糖的内化过程中，嗜天青颗粒融合吞噬体和HCK被激活并易位到吞噬体膜，而在吞噬分枝杆菌的中性粒细胞中，HCK没有易位，保持未激活状态。酪氨酸激酶Fgr的活化不受影响。这些结果表明：1）致病性和非致病性分枝杆菌在中性粒细胞中触发相似的杀菌反应，2）分枝杆菌可以解偶联嗜天青颗粒的吞噬和融合，3）Hck可能是分枝杆菌吞噬过程中改变的嗜天青分泌途径的关键元件之一。
Pathogenic mycobacteria parasitize macrophages and reside within phagosomes, which do not fuse with lysosomal granules. Mycobacteria are also internalized by neutrophils, which possess at least two types of granules, specific and azurophil granules, the latter being specialized lysosomes. Here, we investigated the ability of mycobacteria to inhibit the fusion of these granules with their phagosomes in human neutrophils. It was found that when pathogenic (Mycobacterium kansasii and Mycobacterium avium) or nonpathogenic (Mycobacterium smegmatis and Mycobacterium phlei) mycobacteria were internalized by neutrophils, they induced the inhibition of azurophil granule fusion with phagosomes even when they were serum opsonized. In contrast, secretion of specific granule content and production of O2-, both of which contribute to the neutrophil bactericidal response, were triggered. Hck is a Src family tyrosine kinase associated with azurophil granules. During internalization of zymosan, azurophil granules fused with phagosomes and Hck was activated and translocated to the phagosomal membrane, whereas in neutrophils engulfing mycobacteria, Hck did not translocate and remained unactivated. The activation of the tyrosine kinase Fgr was not affected. These results indicate that 1) pathogenic and nonpathogenic mycobacteria trigger similar bactericidal responses in neutrophils, 2) phagocytosis and fusion of azurophil granules can be uncoupled by mycobacteria, and 3) Hck could be one of the key elements of the azurophil secretory pathway that are altered during phagocytosis of mycobacteria.
影响因子：
4.4
作者：
B. P. Thornton;V. Vetvicka;M. Pitman;R. Goldman;G. D. Ross
通讯作者：
B. P. Thornton;V. Vetvicka;M. Pitman;R. Goldman;G. D. Ross
单核吞噬细胞在结核分枝杆菌发病机制中的作用。
DOI：
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发表时间：
1996
期刊：
Journal of investigative medicine : the official publication of the American Federation for Clinical Research.
影响因子：
--
作者：
Schlesinger,LS
通讯作者：
Schlesinger,LS