Gullberg U, Andersson E, Garwicz D, Lindmark A, Olsson I
Department of Medicine, Research Department 2, University Hospital, Lund, Sweden.
Eur J Haematol. 1997 Mar;58(3):137-53. doi: 10.1111/j.1600-0609.1997.tb00940.x.
Neutrophil granulocytes are specialized phagocytic cells that carry a collection of granules for regulated secretion, each with distinct constituents. The granules can be classified as azurophil (primary), developed first, followed in time by specific (secondary) granules gelatinase granules, and secretory vesicles. Stage- and tissue-specific transcription factors govern the successive expression of genes for granule proteins to allow storage of the gene products in these organelle categories whose packaging is separated in time. Many of the granule proteins, in particular those of the heterogeneous lysosome-like azurophil granules, are subject to extensive post-translational proteolytic processing into mature proteins, most commonly as a post-sorting event. A selective aggregation of proteins destined for storage in granules, as discussed in this review, would facilitate their retention and eliminate a need for distinct sorting motifs on each granule protein. Aggregation of granule proteins, that are often cationic, would be assisted by the anionic serglycin proteoglycans present in neutrophils. The antibacterial granule proteins can serve as models for antibiotics and some of them possess a potentially useful therapeutic ability to bind and neutralize endotoxin. Because aberrant expression of transcription factors regulating the synthesis of granule proteins is often found in leukemia, the clarification of mechanisms regulating the timed expression of granule proteins will shed light on the maturation block in myeloid leukemias.
中性粒细胞是特殊的吞噬细胞，携带一组用于调节分泌的颗粒，每个颗粒都有不同的成分。这些颗粒可分为嗜天青颗粒（初级颗粒），最早形成，随后依次是特异性（次级）颗粒、明胶酶颗粒和分泌小泡。阶段和组织特异性转录因子控制颗粒蛋白基因的相继表达，以便将基因产物储存在这些包装在时间上分开的细胞器类别中。许多颗粒蛋白，特别是那些异质性溶酶体样嗜天青颗粒中的蛋白，在翻译后会经过广泛的蛋白水解加工成为成熟蛋白，最常见的是在分选后发生。如本综述所述，选择性聚集注定要储存在颗粒中的蛋白质将有助于它们的保留，并消除对每个颗粒蛋白上不同分选基序的需求。中性粒细胞中存在的阴离子丝甘蛋白聚糖将有助于聚集通常带阳离子的颗粒蛋白。抗菌颗粒蛋白可作为抗生素的模型，其中一些具有结合和中和内毒素的潜在有用治疗能力。由于在白血病中经常发现调节颗粒蛋白合成的转录因子表达异常，阐明调节颗粒蛋白定时表达的机制将有助于了解髓系白血病中的成熟阻滞。
