Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky-Pudlak syndrome
Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky-Pudlak syndrome
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DOI：
10.1080/13576500600936039
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发表时间：
2007-03-01
期刊：
影响因子：
3.3
通讯作者：
Gahl, William A.
中科院分区：
文献类型：
--
作者：
Huizing, Marjan;Parkes, Jennifer M.;Gahl, William A.
Hermansky-Pudlak综合征（HPS）是一种溶酶体相关的细胞器生物发生障碍，表现为遗传位点异质性。八种已知的HPS蛋白联合收割机结合在功能复合物中，其中两种被称为BLOC-2和BLOC-3; BLOC是溶酶体相关细胞器复合物的生物发生。HPS中受影响的细胞器包括导致色素减退的黑素体和导致出血时间延长的血小板δ（致密）颗粒。整体封片电子显微镜（EM）检测到血小板δ颗粒的缺乏，并确认HPS的诊断。迄今为止，HPS血小板中其他细胞器和颗粒的状态尚未被记录。我们对不同遗传形式的HPS患者的血小板进行了超微结构研究，特别是那些包含BLOC-2和BLOC-3亚型的患者。在我们的患者中，其他血小板细胞器和膜结构的分布、大小或数量没有差异。由于α和δ颗粒是由巨核细胞中的多泡体形成的，并且由于只有δ颗粒在HPS中是有缺陷的，因此我们得出结论，HPS基因在δ颗粒生物发生的一部分中起作用，该部分已经偏离了α颗粒。因此，HPS的全身出血素质不太可能归因于α颗粒的缺乏。
Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis that displays genetic locus heterogeneity. The eight known HPS proteins combine in functional complexes, two of which are called BLOC-2 and BLOC-3; a BLOC is a Biogenesis of Lysosome-related Organelles Complex. Organelles affected in HPS include the melanosome, resulting in hypopigmentation, and the platelet delta (dense) granule, resulting in prolonged bleeding times. Whole mount electron microscopy (EM) detects the absence of platelet delta granules and confirms the diagnosis of HPS. To date, the status of other organelles and granules in HPS platelets has not been documented. We performed ultrastructural studies on platelets of patients with different genetic forms of HPS, specifically those comprising the BLOC-2 and BLOC-3 subtypes. No differences in distribution, size or quantity of other platelet organelles and membrane structures could be detected in our patients. Since alpha and delta granules are formed from multivesicular bodies in the megakaryocyte, and since only delta granules are defective in HPS, we conclude that HPS genes function within the portion of delta granule biogenesis that has diverged from that of alpha granules. Thus, it is unlikely that the generalized bleeding diathesis of HPS is attributed to a deficiency of alpha granules.