User:Heihaheihaha/怀布尔-帕拉德小体
怀布尔-帕拉德小体 (Weibel–Palade bodies, WPBs)又称W-P小体、细管小体，是血管内皮细胞和心脏内膜细胞内的储存颗粒。[1][2] 它们合成、储存并释放两种主要的分子： 血管性血友病因子和P-选择素，因此，W-P小体在止血和炎症中有着重要作用。 [3]
词源[编辑]
W-P小体最早由瑞士解剖学家 Ewald R. Weibel和罗马尼亚生理学家乔治·埃米尔·帕拉德(George Emil Palade)在1964描述。[4] 1974年，帕拉德由于他在研究细胞中细胞器的功能的贡献获得了诺贝尔生理学和医学奖。
组分[编辑]
W-P小体内主要储有两种成分：一种是血管性血友病因子（von Willebrand factor，vWF），这是一种在凝血过程中起主要作用的多聚蛋白质[5]，由于储有长聚合物vWF，W-P小体在电镜下呈长条状；[6]另一种是P-选择素，[7][8]，在静息内皮细胞中P-选择素储存在W-P小体中，在被炎症介质、创伤等因素激活后，迅速在细胞表面表达，尤其是在毛细血管后小静脉中的内皮细胞。P-选择素参与介导白细胞等滚动和粘附。[9]
W-P小体中的其它成分还包括 白介素-8、嗜酸性粒细胞趋化因子-3、内皮素-1、血管生成素-2、骨保护素、P-选择素辅因子CD63/lamp3、[10]和FUT6。
产生[编辑]
多聚体形式的vWF在高尔基体中由尾对尾的vWF二聚体以头对头的方式组装（ D3 结构域之间形成“头对头”链间二硫键）。vWF多聚体凝聚并扭曲成长的螺旋形，大多数平行的微管之间由较稀疏的蛋白质结构域矩阵隔开。[11] 随后，从高尔基体出芽几乎完全由vWF组成的有网格蛋白包被的囊泡。
未成熟的W-P小体停留在靠近细胞核的位置，在那里它们获得更多的膜蛋白，然后在微管和驱动蛋白的帮助下分散到整个细胞质中。[10]网格蛋白包被囊泡从未成熟的W-P小体上出芽，减少了它们的体积，浓缩了其内容物，并移除了一些选择性的膜蛋白。成熟的魏布尔–帕拉德小体也可能相互融合。[11]
唯一在生理学上具有类似功能的细胞器是血小板的α颗粒，它也含有vWF[12]。Weibel–Palade小体是vWF的主要来源，而α颗粒可能只起次要作用。[需要可靠醫學來源]
分泌[编辑]
The small subset of Weibel–Palade bodies tethered at the cell periphery to the actin cortex serve as a readily releasable pool that's replenished by a larger pool of microtubule-associated bodies in the cell interior.[10]
The contents of Weibel–Palade bodies are secreted by one of three mechanisms.[11] Some undergo exocytosis individually, while others fuse transiently to the plasma membrane in a "lingering kiss" that opens a pore large enough for only their smaller cargo (e.g. IL-8, CD63) to diffuse out.[11] Weibel–Palade bodies may also coalesce into larger vesicles called secretory pods for multigranular exocytosis.[11] Secretory pod formation is mediated by interposition of tiny nanovesicles between bodies. As Weibel–Palade bodies fuse with secretory pods, their vWF cargo loses its tubular form for spaghetti-like strings that are then exocytosed through a fusion pore.[11] Whether cargo besides vWF is exocytosed from secretory pods or selectively retained is uncertain. Different modes of cargo release from Weibel–Palade bodies may be a mechanism for differential release of subsets of molecules in different physiological conditions.[11]
在分泌过程中，vWF颗粒融合在一起，形成最后的“长串”。[13]
临床意义[编辑]
一些致病变异凸显了W-P小体的重要性。VWF基因上的变异是血管性血友病的常见病因。血管性血友病在人群中的流行率估计为1%，该病最常见的特征是长期且多变的黏膜和皮肤的出血。类似于严重的A型或B型血友病，III型血管性血友病是一种严重的出血性疾病。VWF 在初级止血过程（形成血小板塞）中起到在受伤部位招募血小板的作用，并且在次级止血过程（形成稳定的纤维蛋白网以加强和巩固血小板塞）中作为凝血因子VIII（FVIII）的伴侣蛋白。 [14][15]
参考文献[编辑]
- ^ Standring, S. Gray's anatomy : the anatomical basis of clinical practice Forty-first. 2016: 132. ISBN 9780702052309.
- ^ Kaufman, Daniel P.; Sanvictores, Terrence; Costanza, Michael. Weibel Palade Bodies. StatPearls. Treasure Island (FL): StatPearls Publishing. 2024. PMID 30570974.
- ^ Valentijn KM, Eikenboom J. Weibel–Palade bodies: a window to von Willebrand disease. Journal of Thrombosis and Haemostasis. April 2013, 11 (4): 581–92. PMID 23398618. doi:10.1111/jth.12160
.
- ^ Weibel ER, Palade GE. New Cytoplasmic Components in Arterial Endothelia. The Journal of Cell Biology. October 1964, 23 (1): 101–12. PMC 2106503 . PMID 14228505. doi:10.1083/jcb.23.1.101.
- ^ Wagner DD, Olmsted JB, Marder VJ. Immunolocalization of von Willebrand protein in Weibel–Palade bodies of human endothelial cells. The Journal of Cell Biology. October 1982, 95 (1): 355–60. PMC 2112360 . PMID 6754744. doi:10.1083/jcb.95.1.355.
- ^ Tuma RF, Durán WN, Ley K (编). Microcirculation 2nd. Amsterdam: Elsevier/Academic Press. 2008: 38. ISBN 978-0-12-374530-9.
- ^ Bonfanti R, Furie BC, Furie B, Wagner DD. PADGEM (GMP140) is a component of Weibel–Palade bodies of human endothelial cells (PDF). Blood. April 1989, 73 (5): 1109–12. PMID 2467701. doi:10.1182/blood.V73.5.1109.1109 .
- ^ McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel–Palade bodies. The Journal of Clinical Investigation. July 1989, 84 (1): 92–9. PMC 303957 . PMID 2472431. doi:10.1172/JCI114175.
- ^ Bullard, D C; Kunkel, E J; Kubo, H; Hicks, M J; Lorenzo, I; Doyle, N A; Doerschuk, C M; Ley, K; Beaudet, A L. Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice.. The Journal of experimental medicine. 1996-05-01, 183 (5). ISSN 0022-1007. doi:10.1084/jem.183.5.2329 （英语）.
- ^ 10.0 10.1 10.2 Doyle EL, Ridger V, Ferraro F, Turmaine M, Saftig P, Cutler DF. CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin. Blood. October 2011, 118 (15): 4265–73. PMID 21803846. doi:10.1182/blood-2010-11-321489 .
- ^ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 Valentijn KM, Sadler JE, Valentijn JA, Voorberg J, Eikenboom J. Functional architecture of Weibel–Palade bodies. Blood. May 2011, 117 (19): 5033–43. PMC 3109530 . PMID 21266719. doi:10.1182/blood-2010-09-267492.
- ^ Blair, Price; Flaumenhaft, Robert. Platelet α–granules: Basic biology and clinical correlates. Blood reviews. 2009-07, 23 (4). ISSN 0268-960X. PMC 2720568 . PMID 19450911. doi:10.1016/j.blre.2009.04.001.
- ^ Lenting PJ, Christophe OD, Denis CV. von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends.. Blood. 26 March 2015, 125 (13): 2019–28. PMID 25712991. S2CID 27785232. doi:10.1182/blood-2014-06-528406 .
- ^ Valentijn KM, Eikenboom J. Weibel-Palade bodies: a window to von Willebrand disease. J Thromb Haemost. April 2013, 11 (4): 581–92. PMID 23398618. doi:10.1111/jth.12160 .
- ^ Pipe, Steven W.; Montgomery, Robert R.; Pratt, Kathleen P.; Lenting, Peter J.; Lillicrap, David. Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A. Blood. 2016-10-20, 128 (16). ISSN 0006-4971. PMC 5073181 . PMID 27587878. doi:10.1182/blood-2016-04-713289 （英语）.
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