Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an unusual anti-angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsis-specific treatment.

Background:The angiogenic growth factor angiopoietin-2 regulates angiogenesis through Tie2 and integrins. Results: An angiopoietin-2 mutant fails to bind to integrin, but not Tie2, and to mediate cell migration. Conclusion: Tie2-independent angiopoietin-2 association with integrin is critical for migration of tumor and endothelial cells. Significance: Understanding the mechanism of angiopoietin-2 interaction with integrin is essential for angiogenesis and cancer invasion.

The polymerizable reduced graphene oxide (mRGO) grafted styrene–acrylonitrile copolymer composites were prepared via free radical polymerization. The graphene oxide (GO) and reduced graphene oxide (rGO) was reacted with 3-(tri-methoxysilyl)propylmethacrylate (MPS) and used as monomer to graft styrene and acrylonitrile on its surface. The successful modification and reduction of GO was confirmed using Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analyzer (TGA), Raman and X-ray diffraction (XRD). The mRGO was prepared using chemical and solvothermal reduction methods. The effect of the reduction method on the composite properties and nanosheet distribution in the polymer matrix was studied. The thermal stability, electrical conductivity and morphology of nanocomposites were studied. The electrical conductivity of the obtained nanocomposite was very high at 0.7 S/m. This facile free radical polymerization provides a convenient route to achieve excellent dispersion and electrically conductive polymers.