The aim of this study was to determine if xenogeneic platelet phagocytosis can be prevented by minimizing interspecies incompatibilities through expression of human SIRPα on porcine liver sinusoidal endothelial cells (LSEC). Methods: Expression of SIRPα was examined on LSEC by PCR and confocal microscopy. CD47 levels on platelets were examined by flow cytometry, as was binding of the extracellular domains of porcine and human CD47 to porcine cells. Platelet phagocytosis was measured following Alectinib mouse artificial activation by porcine CD47. Phagocytosis of human platelets was examined in porcine LSEC

transiently transfected with human SIRPα. Results: SIRPα is expressed on LSEC. Artificial activation of the pathway using the extracellular domain of porcine SIRPα resulted in less human platelet uptake. Flow cytometry showed that binding differences between human and porcine SIRPα and CD47 exist. Expression of human SIRPα in porcine LSEC lead to decreased human platelet

phagocytosis. Conclusions: Interspecies incompatibilities in CD47-SIRPa signaling contribute to xenogeneic platelet phagocytosis by porcine LSEC. Expression of human SIRPα by porcine cells reduces xenogeneic platelet phagocytosis. www.selleckchem.com/products/mi-503.html These findings are a significant contribution to the development of a pig with an organ suitable for xenotransplantation. Disclosures: The following people have nothing to disclose: Leela L. Paris, Luz M. Reyes, Ray K. Chihara, Richard A. Sidner, Ross L. Blankenship, Susan M. Downey, A. Joseph Tector “
“Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has a proliferative effect on several types of cells. However, the MCE role of HB-EGF on hepatic stellate cells (HSCs) is not clear. The present study is to investigate the regulatory effects of HB-EGF on HSC proliferation and apoptosis. Activated primary rat HSCs and two HSC cell lines (human LX2 and rat T6) were used in this study. Four inhibitors (CRM197 to HB-EGF, AG1478 to epidermal growth factor receptor [EGFR], PD98059 to mitogen-activated

kinase, and LY294002 to phosphatidylinositol 3-kinase) were employed to verify the pathway of HB-EGF on cell proliferation and apoptosis. HB-EGF expression was significantly increased in activated HSCs. HB-EGF increased the expressions of phospho-EGFR and ErbB4 receptors, the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. Consequently, HB-EGF stimulated HSC proliferation and suppressed HSC apoptosis. Each individual inhibitor specifically inhibited the correlated receptor or enzyme and inhibited HSC proliferation and induced its apoptosis. HB-EGF promotes HSC proliferation via activation of the EGFR and ErbB4 receptors and, subsequently, via activation of ERK and Akt. Any blockage in the chain obstructs the flow from HB-EGF to HSC proliferation. Therefore, HB-EGF is a potential therapeutic target in liver fibrosis. “
“In their study, Iavarone et al.