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Dermal Lymph and Lymphatics
Published in Waldemar L. Olszewski, Lymph Stasis: Pathophysiology, Diagnosis and Treatment, 2019
The findings are summarized in the Table 11. Among them the most unique structure is open endothelial junction and scanty or lacking basal lamina (see Figures 19 and 20). However, the superficial lymphangioma shows no open junction and uninterrupted basal lamina. The blood capillary reveals closed junction and uninterrupted basal lamina (see Figure 21). It has been confirmed that the lymphatic capillary contains the erythrocyte in the lumen49 and this intraluminal RBC is not the criterion used to differentiate the two capillaries. There is no Weibel-Palade body found in the endothelial cell of the human lymphatic capillary under normal conditions. However, it is likely that it will be found in the near future. In the pathological skin lymphatic capillary it has been detected.
Endothelium
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
Endothelium is a thin monolayer of polygonal, flattened endothelial cells. The cells are 0.2-0.3 pm thick, and are joined edge-to-edge in a ‘crazy paving’ pattern (Figures 1.11 and 9.2). Each cell contains a small store of Ca2+ in the endoplasmic reticulum, which can be as little as 8 nm or so from the surface. Endothelial cells also have a unique storage organelle, the Weibel-Palade body (Section 9.6).
Molecular therapeutics of hemophilia A and B
Published in Expert Review of Hematology, 2022
Jie Gong, Hao-Lin Wang, Lung-Ji Chang
FVIII is a large and complex protein playing a key role in blood clotting, and its biosynthesis involves complicated post-translational modifications and cofactor interactions driven by Bip as well as other molecular chaperones, and FVIII secretion involves LMAN1–MCFD2-mediated transportation. FVIII is stored in the Weibel-Palade body with vWF and secreted into blood circulation via exocytosis. After separation from vWF, FVIII is activated to exhibit coagulation function.
Small GTPases in platelet membrane trafficking
Published in Platelets, 2019
Tony G. Walsh, Yong Li, Andreas Wersäll, Alastair W. Poole
Within platelets, Ral was found associated with dense granules [85] and can be activated by various platelet agonists in a Ca2+-dependent manner, while studies in endothelial cells support a role for RalA in Weibel Palade body exocytosis [86,87]. Interestingly, it is well characterised that Ral activity is regulated by numerous Ras GTPases, including H-Ras, R-Ras, Rap 1 (A and B), which directly bind to and regulate Ral GEFs, including RalGDS and RGL (1–3) [88]. Proteomic data analysis only supports the expression of RGL2 in murine platelets, while the RalGAP α1, α2 and β subunits are present in human (and mouse) platelets to regulate Ral-GTP hydrolysis [28,89]. Considering the importance of Rap to platelet secretion, if would be interesting to assess a potential crosstalk between Rap and Ral GTPases. Functional studies involving permeabilised human platelets alluded to a role for Rals in dense granule secretion, through an interaction with EXOC2 [90]. However, a recent study from our group demonstrated that murine platelets lacking either RalA or RalB have no defect in dense granule cargo release, while RalA/B double KO (DKO) platelets have only a marginal defect which does not alter functional responses such as aggregation and thrombus formation [91]. Interestingly, platelet surface exposure of P-selectin in DKO platelets was substantially reduced (by ~ 85%) in response to GPVI-mediated platelet activation, whereas the release of an array of soluble α-granule cargo was unaffected. Notably, this exocytic defect in α-granule release of P-selectin was not due to the minor reduction in secreted ADP from dense granules. This also reveals mutually redundant trafficking roles for both Ral proteins in platelets, which corroborates their roles in development and tumorigenesis [80]. These findings raise intriguing questions regarding exocytic trafficking processes in platelets. Firstly, do ‘kiss-and-run’ secretion events occur, where soluble cargo are readily released upon transient fusion of the secretory vesicle at the plasma membrane? An alternative explanation is the presence of P-selectin positive and negative α-granule subpopulations, as it has been reported to be differentially localised to another α-granule protein, vWF, and thereby Rals could specifically target the P-selectin positive population [92]. Undoubtedly many questions remain regarding theories of cargo storage in platelets and mechanisms controlling their trafficking and release, but these observations reported in Ral deficient platelets offer attractive therapeutic potential [93,94].