The Weibel-Palade body: the storage granule for von Willebrand factor and P-selectin

DD Wagner - Thrombosis and haemostasis, 1993 - thieme-connect.com
Thrombosis and haemostasis, 1993thieme-connect.com
Endothelial cells of most blood vessels contain elongated granules called Weibel-Palade
bodies which are not found in any other cell type (Fig. 1)(1). These membrane-bound
organelles can be up to 4 pm long and 0.1 pm thick-therefore large enough to be seen in the
light n~ icroscope. In the electron microscope. longitudinally arranged tubular structures
(Fig. 1) that represent highly organized polymers of the adhesive glycoprotein von
Willebrand factor (vWf) can be distinguished inside the granule (Fig. 1)(2-4). After stimulation …
Endothelial cells of most blood vessels contain elongated granules called Weibel-Palade bodies which are not found in any other cell type (Fig. 1)(1). These membrane-bound organelles can be up to 4 pm long and 0.1 pm thick-therefore large enough to be seen in the light n~ icroscope. In the electron microscope. longitudinally arranged tubular structures (Fig. 1) that represent highly organized polymers of the adhesive glycoprotein von Willebrand factor (vWf) can be distinguished inside the granule (Fig. 1)(2-4). After stimulation of the endothelial cell, vWf is released from the granules into the surrounding blood or basement membrane (for review see 5). M7eibel-Palade bodies therefore are true storage granules such as are found. for example, in hornlone secretory cells. Although we have searched for other soluble components in the Weibel-Palade bodies, ae did not find any other than\, Wf and its propolypeptide. To date. two membrane components of the Weibel-Palacle bodies have been described: the adhesion receptor for phagocytic cells P-selectin (6.7) and. very recently. the lysosomal membrane protein CD63 (8) which\vas localized im~ nunologically (U. Vischer and D. Wagner. manuscript in preparation). vM7f and P-selectin have the same tissue-specific expression since they are synthesized only by endothelial cells and by megakaryocytes. the precursors of platelets. In addition, in both cell types P-selectin and\lWf are found in the same storage granules-the wgranules in platelets (9-12) and Weibel-Palade bodies in endothelium. CD63 is a ubiquitous lysosolnal membrane protein and it is not known whether it is found in storage granules of other cell types. vWf and its prosequence (with which the rnolecule is initially synthesized) are found in Weibel-Palade bodies in stoichiometric amounts: this indicates that the proteolytic cleavage betn-een them likely occurs at the time that the protein is packaged into the Weibel-Palacle body or inside the organelle (13.14). The prosequence of vWf is necessary for the protein mu! timerization by disulfide bonding, since vWf expressed without the prosequence remains dimeric (15.16). We have found that the propolypeptide has sequences similar to those found at the active site of protein disulfide isomerase-the enzyme that catalyses disulfide bond formation in the endo-. plasmic reticulun~. Mutagenesis in these regions through insertion of an extra glq-cine residue completely abolishes the capacity ol'the prosequence to promote multiinerization (17). This indicates that vWf may carry its own multimerizing enzyme (the prosequence) that is activated in the compartments late in the secretory path\va!-.\vhere such activity is
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