Ultrafine Particles Exert Prothrombotic but Not Inflammatory Effects on the Hepatic Microcirculation in Healthy Mice In Vivo

Abstract

Background-Air pollution episodes are strongly associated with increased cardiovascular morbidity and mortality. The effect of ultrafine particles (UFPs), when translocated after inhalation, on the microcirculation of extrapulmonary organs remains unclear. Methods and Results-In C57BL/6 mice, either carbon black UFPs (1ϫ10 7 and 5ϫ10 7 ) or vehicle was infused intra-arterially. Two hours after infusion, platelet-and leukocyte-endothelial cell interactions, sinusoidal perfusion, endothelial fibrin(ogen) deposition, and phagocytic activity of Kupffer cells were analyzed by intravital video fluorescence microscopy in the liver microvasculature. Expression of fibrin(ogen), von Willebrand factor (vWF), and P-selectin on hepatic endothelium was determined by immunostaining. Apoptotic cells were quantified in TUNELstained tissue sections. Application of UFPs caused significantly enhanced platelet accumulation on endothelium of postsinusoidal venules and sinusoids in healthy mice. UFP-induced platelet adhesion was not preceded by platelet rolling but was strongly associated with fibrin deposition and an increase in vWF expression on the endothelial surface. In contrast, inflammatory parameters such as the number of rolling/adherent leukocytes, P-selectin expression/ translocation, and the number of apoptotic cells were not elevated 2 hours after UFP exposure. In addition, UFPs did not affect sinusoidal perfusion and Kupffer cell function. Conclusions-UFPs

CD4+ T cells contribute to postischemic liver injury in mice by interacting with sinusoidal endothelium and platelets

“…Platelet-and leukocyte-endothelial cell interactions as well as sinusoidal perfusion were quantified using intravital microscopy in sham-operated mice, and after I/R (90 min/30-50 min) in wild-type mice, in CD4 Ϫ/Ϫ mice, and in mice lacking either CD40L or CD28 costimulatory molecules (n ϭ 6 each group). In an additional I/R group (n ϭ 6), platelets were inactivated with tirofiban, an antagonist of glycoprotein IIb/IIIa (GpIIb/ IIIa) receptors on platelets (36 g/g bodyweight, 23,24 MSD, Haar, Germany), infused before reperfusion. Activity of AST/ALT was measured in these groups as parameters of hepatocellular injury.…”

Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration

“…For this purpose, platelets were isolated from either wild-type or JAM-A Ϫ/Ϫ mice, labeled ex vivo with rhodamine 6G as described previously, 23,26,27 infused intra-arterially in wild-type mice after 90 minutes of ischemia and 30 minutes of reperfusion, and quantitatively analyzed using intravital microscopy in hepatic sinusoids and postsinusoidal venules as described for leukocytes. Sham-operated JAM-A ϩ/ϩ animals were used as controls.…”

Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation

“…Elevated levels of vWF were observed in association with increased concentrations of particulate matter in patients with coronary heart disease 38 and mice exposed to nanoparticles. 39 Because the thrombosis measured in vivo in our model depends mainly on the intensity of the vascular lesion and subsequent platelet recruitment and aggregation, we aimed at assessing the direct effect of SiNPs on platelet aggregation in whole blood in vitro. Our observations confirmed the occurrence of platelet aggregation following the addition of SiNPs.…”