Weiss H J, Lages B, Vicic W, Tsung L Y, White J G
Department of Medicine, Division of Hematology-Oncology, St. Luke's-Roosevelt Hospital Center, New York, N.Y.
Br J Haematol. 1993 Feb;83(2):282-95. doi: 10.1111/j.1365-2141.1993.tb08284.x.
Studies on platelet dense granule structure were carried out in 20 patients with various types of congenital storage pool deficiency (SPD), including 15 with specific deficiencies of dense granules and dense granule substances (delta-SPD), and five with combined deficiencies of dense and alpha-granules (alpha delta-SPD). Dense granules were identified by their high affinity for uranyl ions (uranaffin reaction), by their ability to accumulate the fluorescent dye mepacrine, and by their inherent electron opacity on unfixed, unstained whole mount preparations. By all these methods, dense granules were markedly decreased in seven albino patients with the Hermansky-Pudlak syndrome (HPS) variant of delta-SPD. These findings suggest that the basic defect in these patients is a specific abnormality in organelle development which prevents the formation of an intact granule structure, a quantitative abnormality which may differ from that in animals with related pigment disorders. In contrast, eight non-albino patients with delta-SPD had, on average, only a slightly reduced number of uranaffin-positive and mepacrine-positive granules, but a shift in uranaffin-granule distribution towards those lacking a dense core ('empty granules'), suggesting a more qualitative type of dense granule defect. These results are consistent with previous evidence suggesting a decreased uptake of ATP across the granule membrane in delta-SPD. In addition, on whole mounts, these patients' platelets contained substantial numbers of electron dense chains and clusters which contained P and Ca, but with a P/Ca ratio less than that of typical dense granules, and which were retained, along with a larger amount of ATP, after thrombin treatment of the platelets. The various findings in these patients raise the possibility that these structures may represent microvesicles, derived from the Golgi apparatus, which provide a transport mechanism for concentrating adenine nucleotides and calcium in dense granules and which is impaired in some patients with SPD. Additional defects may account for the more extensive granule abnormalities observed in alpha delta-SPD.
对20例患有各种类型先天性贮存池病（SPD）的患者进行了血小板致密颗粒结构研究，其中15例患有致密颗粒和致密颗粒物质的特异性缺乏（δ-SPD），5例患有致密颗粒和α-颗粒的联合缺乏（αδ-SPD）。致密颗粒通过其对铀离子的高亲和力（铀黄反应）、积累荧光染料美帕林的能力以及在未固定、未染色的整装制剂上固有的电子不透明度来识别。通过所有这些方法，在7例患有δ-SPD的Hermansky-Pudlak综合征（HPS）变异型的白化病患者中，致密颗粒明显减少。这些发现表明，这些患者的基本缺陷是细胞器发育中的一种特异性异常，它阻止了完整颗粒结构的形成，这是一种定量异常，可能与患有相关色素紊乱的动物不同。相比之下，8例非白化病δ-SPD患者平均仅有略微减少的铀黄阳性和美帕林阳性颗粒，但铀黄颗粒分布向缺乏致密核心的颗粒（“空颗粒”）转移，提示致密颗粒缺陷的性质更具质性。这些结果与先前的证据一致，表明在δ-SPD中跨颗粒膜的ATP摄取减少。此外，在整装制剂上，这些患者的血小板含有大量含磷和钙的电子致密链和簇，但磷/钙比值低于典型致密颗粒，并且在血小板经凝血酶处理后，这些结构与大量ATP一起保留下来。这些患者的各种发现增加了这样一种可能性，即这些结构可能代表源自高尔基体的微泡，它为在致密颗粒中浓缩腺嘌呤核苷酸和钙提供了一种运输机制，并且在一些SPD患者中受损。其他缺陷可能解释了在αδ-SPD中观察到的更广泛的颗粒异常。
