AP112 Sigma-AldrichGoat Anti-Human IgG Antibody

Septic shock is characterized by increased vascular permeability and hypotension despite increased cardiac output. Numerous vasoactive cytokines are upregulated during sepsis, including angiopoietin 2 (ANG2), which increases vascular permeability. Here we report that mice engineered to inducibly overexpress ANG2 in the endothelium developed sepsis-like hemodynamic alterations, including systemic hypotension, increased cardiac output, and dilatory cardiomyopathy. Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to develop hemodynamic alterations. Interestingly, the hemodynamic alterations associated with endothelial-specific overexpression of ANG2 and the loss of capillary-associated pericytes were reversed by intravenous injections of adeno-associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice, which rapidly developed hypotension, acute pericyte loss, and increased vascular permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to 61%. These data indicate that ANG2-mediated microvascular disintegration contributes to septic shock and that inhibition of the ANG2/TIE2 interaction during sepsis is a potential therapeutic target.

Targeted photodynamic therapy (TPDT) involves the administration of a photosensitizer (PS) conjugated with a targeting moiety followed by light activation. The systemic toxicity associated with conventional therapy may thus be significantly reduced in TPDT due to the dual selectivity provided by the spatial localization of the illumination as well as the target-localizing ability of the conjugate. Herein, a photo-immuno-conjugate-associating-liposome (PICAL) for TPDT has been developed in which the FDA approved benzoporphyrin derivative monoacid A (BPD) and the Cetuximab antibody for epidermal growth factor receptor (EGFR) were associated into a stable Preformed Plain Liposome (PPL) by passive physical adsorption. Results have shown that the BPD molecules adsorbed into PICAL have stable optical behavior and a higher fluorescence quantum yield than free-BPD. The Cetuximab adsorbed into PPL selectively binds to cells that overexpress EGFR. The inhibition of EGFR signaling by PICAL has enhanced PDT-mediated ovarian cancer cell death.In this basic science study, a photo-immuno-conjugate-associating-liposome for targeted photodynamic therapy is investigated. The FDA-approved benzoporphyrin derivative monoacid A and an epidermal growth factor receptor antibody were assembed into a stable Preformed Plain Liposome (PPL) by passive physical adsorption. The authors demonstrate therapeutic efficacy of the above construct in an ovarian tumor system.