P. Andre et al., Platelets adhere to and translocate on von Willebrand factor presented by endothelium in simulated veins, BLOOD, 96(10), 2000, pp. 3322-3328
With the use of intravital microscopy, a new type of platelet-endothelial i
nteraction in mouse mesenteric venules at low shear (80-100 seconds(-1)) is
described. Stimulation of these vessels with calcium ionophore A23187, a k
nown secretagogue of Welbel-Palade bodies, induced immediate platelet adhes
ion (within 15 seconds) and translocation without the formation of aggregat
es. This stop-and-go process reached a maximum in approximately 1 minute, w
hen approximately 25 000 platelets adhered/mm(2.)s, and then adhesion progr
essively decreased. This adhesion process was dependent on von Willebrand f
actor (vWF) and independent of P-selectin. Immunohistologic analysis showed
that the venules were not denuded with A23187 treat ment, suggesting that
platelets adhered to VWF secreted on the luminal face of the endothelial ce
lls. Histamine treatment induced a similar adhesion phenomenon. Platelet ad
hesion was not abolished in beta3-deficient mice or when the platelets were
treated with inhibitory antibodies to PECAM-1 or PSGL-1, indicating that t
hese molecules are not required for platelet-endothelium interaction at low
shear, The adhesion was mediated by platelet glycoprotein lb alpha (GPlb a
lpha) because the adhesion of murine platelets expressing exclusively the h
uman GPlb alpha could be prevented by a pretreatment with mocarhagin, a sna
ke venom protease that cleaves human GPlb alpha. The results indicate that
VWF released from Weibel-Palade bodies can dramatically increase the concen
tration of platelets along the vessel wall through an interaction with GPlb
alpha. It is proposed that this process may rapidly recruit platelets to s
ites of injury or inflammation in veins. (C) 2000 by The American Society o
f Hematology.