However, a more complex mutation at the furin cleavage site, deletion 2269_2270delCT, results in alternative splicing across intron 17 and causes persistence of pro-VWF.12,62 When expressed in AtT-20 cells, this variant is targeted to storage granules, in contrast to the R763G mutation, indicating that the persistence of pro-VWF per se does not prevent granular storage. vWF then cross-links basement membrane collagen of the vessel to gp1b seen on platelets. Lingering-kiss exocytosis of WPBs is characterized by the rounding up of the WPBs. (for review see Sadler, 2008). supportTerms and (B) Scanning EM of VWF strings at the surface of stimulated HUVECs displaying numerous branching VWF strings. However, VWF does unfurl within multigranular secretory pods that nevertheless discharge VWF strings on exocytosis, which suggests that the preservation of tubular packaging is not a prerequisite for the assembly of VWF strings. This is accompanied by the BLOC-2 and annexin A8 dependent transfer of endosomal components such as CD63 and VAMP8 to WPB (2). The effects of epinephrine infusion in patients with von Willebrand's disease. One striking characteristic of endothelial cells relates to the adhesive properties of their apical cell surface that faces the blood vessel lumen. Structural organization of Weibel-Palade bodies revealed by cryo - PNAS For simplicity, the release of only 2 different cargo molecules is depicted: membrane-bound P-selectin released into the plasma membrane, and VWF released into the blood, where it can form long strings. An official website of the United States government. (2019). 10.1182/blood-2014-10-608596 [Google Scholar] Nguyen T. T. N., Koerdt S. N., Gerke V. (2020). 1996 Mar;3(1):19-28. doi: 10.3109/10739689609146779. Formation and function of Weibel-Palade bodies Francis C. R., Claflin S., Kushner E. J. Authors Johannes Na 1 , Julian Terglane 1 , Volker Gerke 1 Affiliation This maturation is driven on one hand by the continued multimerization and tight packing of VWF into a quasi-crystalline arrangement enwrapped by a membrane, which requires luminal acidification and reflects itself in the condensation of WPB from an electron lucent immature organelle to an electron dense mature structure. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. They carry a variety of bioactive molecules that are needed to mount a rapid response to the complex environment of cells that line blood vessels. Here, actin framework formation occurs prior to the actual fusion event facilitating WPB exocytosis (Han et al., 2017; Li et al., 2018). Exocytosis of Weibel-Palade bodies: how to unpack a vascular emergency kit. Nitric Oxide Regulates Exocytosis by S-Nitrosylation of N-Ethylmaleimide-Sensitive Factor. use of (2020b). They are found in arteries, capillaries, veins, and the endocardium, but notably not in the lymphatic vessels. PMC Weibel-Palade bodies: secretory organelles of the endothelium The main cargo of Weibel-Palade bodies (WPBs) is von Willebrand factor (VWF), which is a large multimeric adhesive protein that mediates platelet adhesion to the endothelium and to the subendothelial matrix 1, 2. Please enable it to take advantage of the complete set of features! Moreover, through selective secretion and uptake as well as production and decoding of signaling molecules they regulate blood vessel homeostasis including clotting and coagulation, fibrinolysis and thrombosis as well as vascular tone and local inflammatory reactions. The role of the D1 domain of the von Willebrand factor propeptide in multimerization of VWF. Elongated WPB morphology is correlated to longer VWF strings with better adhesive properties. Rab27A and Rab3B/D, the former required for linking WPB at the cortical actin cytoskeleton (via MyRIP/MyoVc) and supporting exocytosis (via Slp4-a) (3). Holthenrich A., Drexler H. C. A., Chehab T., Na J., Gerke V. (2019). The G12E polymorphism in the AVPR2 increases its affinity for vasopressin approximately 3-fold and is associated with increased plasma levels of VWF and factor VIII.98 Meta-analysis of 5 genome-wide association studies identified polymorphisms in syntaxin-binding protein 5 and syntaxin-2 that are associated with VWF and factor VIII levels.99 These proteins have not been implicated previously in the release of WPBs, but they interact with SNARE complex proteins that do participate such as SNAP23 and syntaxin 4,100 suggesting that syntaxin-binding protein 5 and syntaxin-2 could be considered for such a role.99. The https:// ensures that you are connecting to the Clathrin-coated profiles on the secretory pods suggest remodeling via a clathrin-mediated pathway. Differential Cargo Mobilisation within Weibel-Palade Bodies after Transient Fusion with the Plasma Membrane. Blood outgrowth endothelial cells from Hermansky-Pudlak syndrome patients carrying the AP3B1 mutation also lack CD63 in their WPB indicative of improper organelle maturation. Elongated WPB morphology is correlated to longer VWF strings with better adhesive properties. Several aspects of WPB size control and maturation have been addressed recently revealing novel and exciting connections. Rab27a and MyRIP Regulate the Amount and Multimeric State of VWF Released from Endothelial Cells. Please enable Cookies and reload the page. Sci Rep. 2016 Aug 31;6:32473. doi: 10.1038/srep32473. The role of von Willebrand factor in thrombus formation. Following cortical release and in preparation of PM fusion, WPB are most likely tethered or docked at the membrane. Moreover, the precise function of the actin structures also needs further attention. These bodies function to store two principal molecules, P-selectin and Von Willebrand factor. This review will discuss aspects of WPB biogenesis, trafficking and exocytosis focussing on recent findings describing factors contributing to WPB maturation, WPB-actin interactions and WPB-plasma membrane tethering and fusion. Leebeek F. W. G., Eikenboom J. C. J. van Breevoort D., van Agtmaal E. L., Dragt B. S., Gebbinck J. K., Dienava-Verdoold I., Kragt A., et al. Careers. The vascular endothelium consists of a very flat monolayer of cellsthe thickness of capillary endothelial cells ranges between 0.17 and 0.23 m.87 Elongated WPBs usually align parallel to the cell membrane, which preserves the flatness of the endothelium. The Weibel-Palade body (WPB) is one of the lysosome-related organelles (LROs) in endothelial cells, whose main content is von Willebrand factor (vWF). As a consequence, this also reduces the pro-thrombotic activity of secreted VWF as VWF secretion from shorter WPB significantly dampens its platelet adhesion capability (Ferraro et al., 2016, 2020). Rojo Pulido I., Nightingale T. D., Darchen F., Seabra M. C., Cutler D. F., Gerke V. (2011). Mietkowska M., Schuberth C., Wedlich-Sldner R., Gerke V. (20191866). and transmitted securely. Biogenesis and Exocytosis of Weibel-Palade Bodies. The remarkable architecture of WPBs is because of the unique properties of their major constituent VWF. The different consequences of disrupting VWF tubules in monensin-treated WPBs and in multigranular secretory pods may be reconciled by considering the time scales of these phenomena. An official website of the United States government. A new look at Weibel-Palade body structure in endothelial cells using electron tomography. WPBs are indicated by asterisks. Tuning the endothelial response: differential release of exocytic cargos from Weibel-Palade bodies. A central role for Rab27a in this event has been shown by Bierings and coworkers (Bierings et al., 2012) who reported that the evoked release of mature WPB is regulated by the interaction of Rab27a with either MyRIP (supporting cortical anchorage) or synaptotagmin-like protein 4-a (Slp4-a) (promoting WPB exocytosis) (Figure 1). Chehab T., Santos N. C., Holthenrich A., Koerdt S. N., Disse J., Schuberth C., et al. Recombinant factor VIII expressed in human endothelial cells was stored with VWF and caused the endogenous WPBs to become spherical.57 Unexpectedly, several VWD type 2N mutations that markedly impair factor VIII-VWF binding did not prevent the storage of factor VIII with VWF in HEK293 cells, and both proteins were stored in spherical organelles.57 This apparently paradoxical result suggests that factor VIII might bind more tightly to VWF type 2N variants in the TGN (pH 6.2) than in standard factor VIII-VWF binding assays (pH 7.4). STXBP1 Promotes Weibel-Palade Body Exocytosis through its Interaction with the Rab27A Effector Slp4-A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases. A., Romani de Wit T., Voorberg J. Ferraro F., Patella F., Costa J. R., Ketteler R., KristonVizi J., Cutler D. F. (2020). Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Clearly, more work is required to establish a potential link between this zyxin/actomyosin network and the post-fusion actin rings, e.g. eCollection 2023. Interaction between MyRIP and the Actin Cytoskeleton Regulates Weibel-Palade Body Trafficking and Exocytosis. Syntaxin-3 interacts with VAMP8, another WPB-associated v-SNARE, but interestingly, was shown to localize mainly to WPB (Schillemans et al., 2018, 2019). Almost 20 years later WPBs were shown to contain von Willebrand factor (VWF),4 a multimeric hemostatic protein that is secreted into the blood in response to a variety of agonists and mediates platelet adhesion at sites of vascular injury. (2020). Epub 2016 Dec 22. the proinflammatory P-selectin, is released (Miteva et al., 2019) (Figure 1). Treasure Island (FL): StatPearls Publishing; 2023 Jan. Would you like email updates of new search results? J Cell Biol. Weibel Palade Bodies: Unique Secretory Organelles of Endothelial Cells Scale bar, 200 nm. High-pressure freezing provides insights into Weibel-Palade body biogenesis. Assembly of Weibel-Palade body-like tubules from N-terminal domains of von Willebrand factor. Interestingly, P-selectin is also produced by platelets and is recruited to the -granule.26 Although VWF and P-selectin are specific for the WPBs and -granules, deficiency of VWF disrupts the targeting of P-selectin to endothelial WPBs but has no effect on targeting P-selectin to platelet -granules. The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells. Biochim. Formation and function of Weibel-Palade bodies - PubMed Along these lines, Ferraro and coworkers developed a microscopic screening approach measuring WPB size that led to the identification of first candidate compounds that reduce WPB length. (2021). Unable to load your collection due to an error, Unable to load your delegates due to an error. Blood 125, 3509-3516. Blood. Inhibition of N-ethylmaleimide-sensitive factor protects against myocardial ischemia/reperfusion injury. The exocyst complex in polarized exocytosis. Upon demand, VWF is secreted into the blood circulation, where it unfolds into strings that capture platelets during the onset of primary hemostasis. Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP. Elsevier B.V. or its licensors or contributors. Molecular components regulating WPB excytosis. The partially emptied and rounded WPBs are presumed to retract from the plasma membrane, but their fate is unknown. (A) Immunofluorescence image of a stimulated HUVEC labeled with an antibody against VWF showing numerous VWF strings branching at the surface of the cell. Integrin alpha(v)beta(3) on human endothelial cells binds von Willebrand factor strings under fluid shear stress. Mutations C1157F and C1234W of von Willebrand factor cause intracellular retention with defective multimerization and secretion. The adjacent VWF sequence is 521CGLCGNYN528, and the N528S substitution may allow the glycosylation of Asn526. Thus, WPB are pivotal components of the precisely tuned machinery that orchestrates blood vessel homeostasis. Epub 2018 Jun 7. A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells. Heterogeneous distribution of Weibel-Palade bodies and von Willebrand factor along the porcine vascular tree. (2002). Sharda A. V., Barr A. M., Harrison J. (2019a). 2013 May 3;288(18):13046-56. doi: 10.1074/jbc.M112.441261. The content of multiple exocytosed WPBs may contribute to the formation of VWF strings. 2023 Jan 1;13(1):125-147. doi: 10.7150/thno.78164. Small GTP-binding protein RalA associates with Weibel-Palade bodies in endothelial cells. In HEK293 cells, both VWF C788R and VWF C1225G were stored in WPBs that were somewhat shorter, but tubular packing appeared normal.52, The effect of factor VIII on WPB biogenesis suggests a mechanism by which proteins that interact with VWF may disrupt tubular packing. (A-B) Immunogold localization of CD63 on WPBs. National Library of Medicine The VWF tubules appear discontinuous or kinked at these junctions, suggesting they may be flexible, and video microscopy of living endothelial cells confirms that WPBs do frequently flex at such bends.23,46 Some images show electron dense material between juxtaposed WPBs or focal narrowing at the site of bending, which suggests that complex irregular shapes result from homotypic fusion between WPBs.3 This form of homotypic fusion that occurs in the absence of regulated exocytotic activity (see Exocytosis) most likely represents a maturation step during WPB biogenesis. How to roll an endothelial cigar: the biogenesis of Weibel-Palade bodies. Weibel-Palade bodies (WPBs) are elongated secretory organelles specific to endothelial cells that contain von Willebrand factor (VWF) and a variety of other proteins that contribute to inflammation, angiogenesis, and tissue repair. MADD serves as a GEF for these Rabs and silencing of MADD through knockdown approaches markedly reduced the recruitment of Rab27a, Rab3b and Rab3d to maturing WPB (Figure 1). Lifecycle of Weibel-Palade bodies - PubMed Once early WPB have emerged from the Golgi they acquire additional proteins (and presumably also lipids) in the process of maturation that is accompanied by a microtubule-dependent movement to the cell periphery (for review see McCormack et al., 2017). Neurosurg Clin N Am. Weibel-Palade Body - an overview | ScienceDirect Topics Endothelial Cell "Memory" of Inflammatory Stimulation: Human Venular Scheme depicting the WPB itinerary in endothelial cells. Depletion of BLOC-2 results in both, compromised LEL-to-WPB transport of CD63 and general WPB maturation defects with the WPB appearing round instead of elongated and clustered in the perinuclear region (Figure 1). Blood. Marked progress in understanding their biogenesis, intracellular transport and secretion has been made in the last decade revealing fascinating cell biological phenomena that drive the formation of the organelle and its many modes of exocytosis. The Interplay between the Rab27A Effectors Slp4-A and MyRIP Controls Hormone-Evoked Weibel-Palade Body Exocytosis. FOIA Rab46 Integrates Ca2+ and Histamine Signaling to Regulate Selective Cargo Release from Weibel-Palade Bodies. Morphology of WPBs in nonstimulated cells. Weibel-Palade bodies, organelles of storage and secretion in endothelial cells, harbor a range of bioactive substances, including von Willebrand factor, angiopoietin 2, and interleukin 8. As the Rab46 negative, P-selectin containing WPB exocytose under these conditions, only a fraction of the WPB cargo, e.g. Right, arrangement of the different domains within the helix. Introduction: lysosome-related organelles. (2011). Weibel-Palade bodies (WPBs) are secretory organelles used for post-synthesis storage in endothelial cells that can, very rapidly, be triggered to release their contents. Whereas earlier studies had identified the Ca2+/phospholipid-binding protein annexin A8 as a LEL-localized component of the machinery facilitating LEL-to-WPB delivery of CD63 (Poeter et al., 2014), Sharda and coworkers (Sharda et al., 2020) recently reported the participation of biogenesis of lysosome related organelle-2 (BLOC-2), a protein that can be mutated in the recessive bleeding disorder Hermansky-Pudlak syndrome. MC_U122665003/MRC_/Medical Research Council/United Kingdom. Storage in WPBs also is restored by changing Thr869 in the D3 domain of human mature VWF to Ala, matching the sequence of canine VWF at this position. Many secretagogues that mediate release of WPBs act on G protein-coupled receptors that trigger 1 of 2 major signaling pathways.10 Several agonists, including thrombin and histamine, increase intracellular free Ca2+ through a phospholipase C-dependent mechanism, whereas other agonists such as epinephrine and vasopressin increase intracellular cyclic adenosine monophosphate (cAMP). 2017 Jul;15(7):1285-1294. doi: 10.1111/jth.13696. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Weibel-Palade bodies (WPBs) are the storage organelles for von Willebrand factor (VWF) in endothelial cells. 1982; 95: 355-360. 2018 Jul;38(7):1549-1561. doi: 10.1161/ATVBAHA.117.310701. WPB are generated in a range of sizes, with the largest granules over ten times the size of the smallest. Disclaimer. Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells. (2016). A GBF1-dependent Mechanism for Environmentally Responsive Regulation of ER-Golgi Transport. The https:// ensures that you are connecting to the A copacking of these quanta occurs in the TGN prior to or concomitant with the actual budding of immature WPB which can maintain connections to the Golgi for 24h (Zenner et al., 2007; Ferraro et al., 2014; Mourik et al., 2015). Microcirculation. Bonfanti R., Furie B., Furie B., Wagner D. (1989). More data on the origin and composition of nanovesicles will be needed to assess their role in multigranular exocytosis. The small amount that reaches the Golgi is targeted to spherical granules with disordered tubular packing of VWF.52 These domain D1 mutations indicate that targeting to storage vesicles does not require VWF multimerization, which involves the formation of intersubunit disulfide bonds between D3 domains. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. Conte I. L., Hellen N., Bierings R., Mashanov G. I., Manneville J.-B., Kiskin N. I., et al. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. (C-E) Digital slices through electron tomograms of WPBs displaying irregular shapes suggesting homotypic fusion between WPBs.3 (C) The delimiting membrane of the WPB is not straight along the long axis of the WPB. Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells. In this Cell Science at a Glance and the accompanying poster, we discuss the emerging mechanisms by which WPB size is controlled and how this affects the ability of this organelle to modulate haemostasis. Bethesda, MD 20894, Web Policies Thomas Daniel Nightingale, Queen Mary University of London, United Kingdom. By continuing you agree to the the tetraspanin and P selectin cofactor CD63) and most likely routed to the organelle by direct transport possibly involving tubular carriers. Membrane fusion: grappling with SNARE and SM proteins. 2011 May 12;117(19):5033-43. doi: 10.1182/blood-2010-09-267492. The https:// ensures that you are connecting to the Before Cel Res. Morphology of VWF strings. by identifying the factor(s) promoting actin polymerisation into the ring/coat-like structures at fused WPB. Exocytosis of Weibel-Palade bodies: how to unpack a vascular emergency Moreover, the exocyst complex was identified as a target of BLOC-2 in endothelial cells and exocyst depletion or inhibition phenocopied the WPB maturation defects seen in BLOC-2 deficient cells. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Critical independent regions in the VWF propeptide and mature VWF that enable normal VWF storage. HHS Vulnerability Disclosure, Help We use cookies to help provide and enhance our service and tailor content and ads. (2012). Cleavage of pro-VWF after Arg763 occurs in the TGN and is required for the high-affinity binding of factor VIII to VWF. A.V., and J.V. To do so, vascular endothelial cells are equipped with unique secretory organelles that store among other things leukocyte and platelet adhesion receptors to be released on demand. PMC Weibel-Palade bodies (WPBs) are secretory organelles used for post-synthesis storage in endothelial cells that can, very rapidly, be triggered to release their contents. VWF is synthesized in megakaryocytes and endothelial cells, and is stored and secreted from platelet alpha granules and Weibel-Palade bodies of endothelial cells. Real-time imaging of the dynamics and secretory behavior of Weibel-Palade bodies. A patient with the homozygous VWF N528S mutation did not respond to desmopressin (DDAVP; Rhone Poulenc Rorer, now Aventis Pharma) with an increase in plasma VWF, which suggests that failure to store mutant VWF N528S in transfected cells correlates with failure of storage and regulated secretion in vivo.54, Heterozygous D3 domain mutations C1157F and C1234W were identified in 2 families with VWD type 2A.55 When expressed in COS-7 cells, both mutant proteins were mostly retained in the ER and had severe defects in multimer assembly, which is often observed for VWF mutations at conserved Cys residues. Figure 1. VWF tubules can be assembled reversibly in vitro with the same N-terminal domains of VWF.48 At pH 7.4, similar to the ER, 2 D1D2 propeptides and one disulfide-linked dimeric DD3 fragment form a calcium ion-dependent complex. Bethesda, MD 20894, Web Policies eCollection 2022 Oct. El-Mansi S, Robinson CL, Kostelnik KB, McCormack JJ, Mitchell TP, Lobato-Mrquez D, Rajeeve V, Cutillas P, Cutler DF, Mostowy S, Nightingale TD. Epub 2005 Aug 8. Weibel-Palade bodies: a window to von Willebrand disease GBF1 can be activated by phosphorylation by AMP-activated protein kinase (AMPK), a key enzyme coupling metabolic changes to cellular signaling, and it was shown that low glucose levels and subsequent AMPK activation lead to GBF1 phosphorylation and a resulting upregulation of anterograde VWF trafficking. An official website of the United States government. Several Ca2+ binding proteins have been implicated in coupling these Ca2+ signals to regulated WPB exocytosis, including the above-mentioned Slp4-a, AnxA2 and Munc13-4 as well as another Munc13 family member, Munc13-2 (Zhou et al., 2016; Holthenrich et al., 2019); however, the actual WPB-associated Ca2+ sensor that could directly activate the SNARE machinery most likely is a member of the synaptotagmin family. (2021). Differential recruitment of cargo proteins to WPBs, slow recruitment of membrane proteins during WPB maturation, and tissue-specific differences in endothelial cell phenotype lead to a heterogeneous population of WPBs.2,40 These processes contribute to the emerging concept of WPB plasticity, which can enable specialized secretory responses depending on the applied stimulus, recent history and location of the cell.10. Zhou H. J., Qin L., Zhang H., Tang W., Ji W., He Y., et al. Failure to produce correctly matured VWF and release it through regulated WPB exocytosis results in pathologies, most importantly von-Willebrand disease, the most common inherited blood clotting disorder. 2000; 1: 783-793. Furthermore, it was shown that these structures, in an active myosin motor-dependent process, are required for the efficient release of highly multimeric VWF cargo from the fused WPB (Nightingale et al., 2011). SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock. Transfection with dominant-negative Rab3D (T36N or N135I) causes WPBs to disappear.43 These results suggest that Rab3D inhibits exocytosis and controls the formation and shape of WPBs, consistent with studies of Rab3D knockout mice showing that Rab3D is involved in the biogenesis of pancreatic secretory granules.45 In contrast, transfection with constitutively active RalA (G23V) promotes exocytosis and leads to the disappearance of most WPBs.41,42 These findings indicate that the biogenesis and function of WPBs require the coordinated activity of multiple small GTPases. Rab-genome Analysis Reveals Novel Insights in Weibel-Palade Body Exocytosis. Middle, cutaway view shows the inner diameter of the tubule of 12 nm. The efficiency of sorting to WPBs was determined for tPA, IL-8, monocyte chemoattractant protein-1, and growth regulated oncogene- in comparison with enhanced green fluorescent protein, a nonmammalian protein with no intrinsic targeting information. Traffic. Ultrastructure of tubular body in the endothelial cells of the ocular blood vessels. How to Roll an Endothelial Cigar: The Biogenesis of Weibel-Palade Bodies. Multimerization and storage were not always studied in the same cells, but no discordance among cell lines has been observed for VWF multimerization. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. V-ATPase V0a1 promotes Weibel-Palade body biogenesis through the regulation of membrane fission. They carry a variety of bioactive molecules that are needed to mount a rapid response to the complex environment of cells that line blood vessels. Scale bars, 40 nm. The packing of VWF into tubules does not require dimerization of pro-VWF subunits in the ER. Compound exocytosis and cumulative fusion in eosinophils. McCormack J. J., Lopes da Silva M., Ferraro F., Patella F., Cutler D. F. (2017). Thus, several SNARE complexes are likely to support heterotypic and homotypic WPB fusion events that characterize the final steps in regulated exocytosis. Ferraro F, Mafalda Lopes da S, Grimes W, Lee HK, Ketteler R, Kriston-Vizi J, Cutler DF. Common to these events is their regulation by signaling mediators, in the case of Ca2+-dependent exocytosis the elevated Ca2+ concentrations. A revised model for the secretion of tPA and cytokines from cultured endothelial cells. Please enable it to take advantage of the complete set of features! 2002 Feb;117(2):113-22. doi: 10.1007/s00418-001-0368-9. cookies. WPBs are endothelial cell-specific secretory organelles that, together with a long list of inflammatory and angiogenic mediators, store the hemostatic protein von Willebrand factor (VWF) as their main cargo.
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