Azurophilic granules of human neutrophilic leukocytes are deficient in lysosome-associated membrane proteins but retain the mannose 6-phosphate recognition marker
Azurophilic granules of human neutrophilic leukocytes are deficient in lysosome-associated membrane proteins but retain the mannose 6-phosphate recognition marker
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DOI：
10.1182/blood.v91.3.1044.1044_1044_1058
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发表时间：
1998-02-01
期刊：
影响因子：
20.3
通讯作者：
Bainton, DF
中科院分区：
文献类型：
--
作者：
Cieutat, AM;Lobel, P;Bainton, DF
在骨髓（BM）中粒细胞分化期间，嗜中性白细胞前体合成大量溶酶体酶。这些酶被隔离到嗜天青储存颗粒中，直到几天后用于消化白细胞迁移到发炎组织后被吞噬的微生物。这种嗜天青颗粒群以前被定义为初级溶酶体，即含有未进入消化事件的酸性水解酶的膜结合细胞器。在这项研究中，嗜天青颗粒被纯化，并显示含有大量的甘露糖6-磷酸含糖蛋白（Man 6-P GP），但几乎没有溶酶体相关膜蛋白（LAMP）。此外，在人BM和血液中成熟的各个阶段研究了Man 6-P GP和LAMP的精细结构定位。Man 6-P GP在成熟的所有阶段都存在于嗜天青颗粒内，并且存在于典型的多泡体（MVB）以及多层隔室（MLC）中，通过其内容物的内部膜的同心阵列来鉴定。LAMP在所有鉴定的颗粒群中均不存在，但在囊泡、MVB和MLC的膜中一致发现。后一个隔室以前在这种细胞类型中没有描述过。总之，含有丰富的溶酶体酶和Man 6-P GP的嗜天青颗粒缺乏LAMP糖蛋白。根据目前的标准，它们因此不能被归类为溶酶体，而是可能具有调节分泌物/颗粒的功能特征。相反，静息中性粒细胞的真正溶酶体可能是MVB和MLC。最后，在其他细胞中描述的典型的“致密体”或成熟溶酶体在静息中性粒细胞中不存在。(C)1998年，美国血液学会。
During granulocyte differentiation in the bone marrow (BM), neutrophilic leukocyte precursors synthesize large amounts of lysosomal enzymes. These enzymes are sequestered into azurophilic storage granules until used days later for digestion of phagocytized microorganisms after leukocyte emigration to inflamed tissues. This azurophil granule population has previously been defined as a primary lysosome, ie, a membrane-bound organelle containing acid hydrolases that have not entered into a digestive event. In this study, azurophil granules were purified and shown to contain large amounts of mannose 6-phosphate-containing glycoproteins (Man 6-P GP) but little lysosome-associated membrane proteins (LAMP). In addition, the fine structural localization of Man 6-P GP and LAMP was investigated at various stages of maturation in human BM and blood. Man 6-P GP were present within the azurophilic granules at all stages of maturation and in typical multivesicular bodies (MVB) as well as in multilaminar compartments (MLC), identified by their content of concentric arrays of internal membranes. LAMP was absent in all identified granule populations, but was consistently found in the membranes of vesicles, MVB, and MLC. The latter compartment has not been previously described in this cell type. In conclusion, the azurophilic granules, which contain an abundance of lysosomal enzymes and Man 6-P GP, lack the LAMP glycoproteins. By current criteria, they therefore cannot be classified as lysosomes, but rather may have the functional characteristics of a regulated secretor/granule. Rather, the true lysosomes of the resting neutrophil are probably the MVB and MLC. Finally, the typical "dense bodies" or mature lysosomes described in other cells are not present in resting neutrophils. (C) 1998 by The American Society of Hematology.