Gullberg U, Bengtsson N, Bülow E, Garwicz D, Lindmark A, Olsson I
Department of Hematology, Research Department 2, E-blocket, University Hospital, S-221 85, Lund, Sweden.
J Immunol Methods. 1999 Dec 17;232(1-2):201-10. doi: 10.1016/s0022-1759(99)00177-5.
Neutrophils contain an assembly of granules destined for regulated secretion, each granule type with distinct constituents formed before terminal differentiation. The earliest granules are designated azurophil (primary), followed in time by specific (secondary), and gelatinase granules as well as secretory vesicles. Transcription factors regulate the genes for the granule proteins to ensure that expression of the gene products to be stored in different organelles is separated in time. Similar to lysosomal enzymes, many granule proteins, in particular those of the heterogeneous azurophil granules, are trimmed by proteolytic processing into mature proteins. Rodent myeloid cell lines have been utilized for research on the processing and targeting of human granule proteins after transfection of cDNA. Results from extensive work on the hematopoietic serine proteases of azurophil granules, employing in vitro mutagenesis, indicate that both an immature and a mature conformation are compatible with targeting for storage in granules. On the other hand, the amino-terminal propeptide of myeloperoxidase facilitates both the export from the endoplasmic reticulum and targeting for storage in granules. Similarly, targeting of defensins rely on an intact propeptide. The proteolytic processing into mature granule protein is most commonly a post-sorting event. Mis-sorting of specific granule proteins into azurophil or lysosome-like granules can result in premature activation and degradation, but represents a potential for manipulating the composition and function of neutrophil granules.
中性粒细胞含有一系列用于调节分泌的颗粒，每种颗粒类型在终末分化前形成具有不同成分的颗粒。最早的颗粒被称为嗜天青颗粒（初级颗粒），随后依次是特异性颗粒（次级颗粒）、明胶酶颗粒以及分泌小泡。转录因子调控颗粒蛋白的基因，以确保储存于不同细胞器中的基因产物的表达在时间上是分开的。与溶酶体酶类似，许多颗粒蛋白，特别是那些异质性嗜天青颗粒中的蛋白，通过蛋白水解加工被修剪成成熟蛋白。在转染cDNA后，啮齿动物髓系细胞系已被用于研究人类颗粒蛋白的加工和靶向。利用体外诱变对嗜天青颗粒的造血丝氨酸蛋白酶进行的大量研究结果表明，未成熟和成熟构象都与靶向储存于颗粒中兼容。另一方面，髓过氧化物酶的氨基末端前肽既有助于从内质网输出，也有助于靶向储存于颗粒中。同样，防御素的靶向依赖于完整的前肽。蛋白水解加工成成熟颗粒蛋白最常见的是分选后事件。特异性颗粒蛋白错误分选到嗜天青颗粒或溶酶体样颗粒中可导致过早激活和降解，但这也为操纵中性粒细胞颗粒的组成和功能提供了可能性。
