Disease relevance of Weibel-Palade Bodies

• We now show that S1P activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation [1].
• Rickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies [2].

High impact information on Weibel-Palade Bodies

• Endothelial cells therefore concentrate a special subclass of very large and biologically potent vWf multimers in Weibel-Palade bodies, presumably available for release in response to vascular injury [3].
• In turn, the antagonistic ligand Ang-2 acts by an autocrine mechanism and is stored in endothelial Weibel-Palade bodies from where it can be rapidly released upon stimulation [4].
• Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells [5].
• During acute inflammation, P-selectin is transiently mobilized from Weibel-Palade bodies to the surface of histamine-activated endothelial cells, where it mediates rolling adhesion of neutrophils under hydrodynamic flow [6].
• IL-4 or OSM increased P-selectin protein on the cell surface as well as in Weibel-Palade bodies [6].

Biological context of Weibel-Palade Bodies

• Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation [7].
• Storage of a fucosyltransferase in Weibel-Palade bodies suggests a function independent of Golgi-associated glycosylation [8].
• After endocytosis, P-selectin is either sorted via endosomes and the Golgi apparatus for storage in Weibel-Palade bodies or targeted to lysosomes for degradation [9].
• Our findings indicate that although P-selectin and CD63 are both targeted to the same compartments from the PM, the kinetics and the ratio of their targeting to Weibel-Palade bodies versus lysosomes are very different [10].
• P-selectin (CD62P), a cell adhesion molecule for most leukocytes, is stored in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells [11].

Anatomical context of Weibel-Palade Bodies

• In the endothelial cell, part of the vWF multimers is stored in specialized organelles, the Weibel-Palade bodies [12].
• We conclude that the presence of activated platelets in circulation promotes acute inflammation by stimulating secretion of Weibel-Palade bodies and P-selectin-mediated leukocyte rolling [13].
• Analysis of subcellular fractions of endothelial cells metabolically labeled with sulfate showed that both cleavage and covalent multimerization occur after sulfation and precede the formation of Weibel-Palade bodies [14].
• Immunohistochemical analysis and transmission electron microscopy of the ESE showed characteristics associated with the microvasculature in vivo (von Willebrand factor, Weibel-Palade bodies, basement membrane material, and intercellular junctions) [15].
• By immunofluorescent staining, P-selectin antibody was first seen in endosomes, then in the Golgi region, and finally in Weibel-Palade bodies [16].

Associations of Weibel-Palade Bodies with chemical compounds

• These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen [17].
• They were not as slowly migrating in a very porous 0.5% agarose gel system as the ULvWF multimers released from Weibel-Palade bodies in response to the calcium ionophore A23187 [18].
• Desmopressin, (DDAVP; 1-desamino-8-D-arginine vasopressin) increases the release and activity of von Willebrand factor (vWF); however, its effects on the other major constituent of endothelial Weibel-Palade bodies, P-selectin, has not been investigated [19].
• These cells share certain common features including monolayer formation, production of Factor VIII antigen, production of prostacyclin, and presence of Weibel-Palade bodies [20].
• When cells are treated with U18666A, a drug that mimics the Niemann-Pick type C syndrome, both proteins accumulate in late endosomes and fail to reach Weibel-Palade bodies efficiently, suggesting that P-selectin, like CD63/lamp3, cycles via late endosomes [21].

Gene context of Weibel-Palade Bodies

• We show that mutant Rab3D proteins interfere with the formation of bona fide Weibel-Palade bodies (WPbs), the principal storage granules of multimeric vWF, and consequently the acute, histamine-induced release of vWF [22].
• Our results indicate that CD63 colocalizes with vWF and P-selectin in the Weibel-Palade bodies of endothelial cells, and together with these adhesion proteins it could be rapidly expressed on the cell surface in areas of vascular injury and inflammation [23].
• We have previously shown endothelin (ET)-like immunoreactive staining in Weibel-Palade bodies, storage granules that are an integral component of the regulated secretory pathway in endothelial cells [24].
• Costaining with P-selectin showed that storage of Ang-2 and P-selectin in Weibel-Palade bodies is mutually exclusive [25].
• Moreover, thrombin-induced rapid mobilization of P-selectin from Weibel Palade bodies was not p38 MAPK dependent [26].

Analytical, diagnostic and therapeutic context of Weibel-Palade Bodies

• Confocal microscopy studies revealed that PAR2 and forskolin caused preferential release of a population of Weibel-Palade bodies (WPBs) consisting of only VWF [27].
• Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles [28].
• These granules could, moreover, be visualized with fluorochrome-coupled Ricinus communis agglutinin I (RCA), which also stained the Golgi apparatus as a reticular juxtanuclear structure, and they were identified as Weibel-Palade bodies by immunoelectron microscopy [29].
• Confirmation of its endothelial origin is achieved by positive staining for Factor VIII-related antigen or by the demonstration of Weibel-Palade bodies by electron microscopy [30].

References