Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Role of angiopoietin-1 and angiopoietin-2 during group A streptococcal infections: clinical and human endothelial cell studies (#213)

Ching-Chuan Liu 1 , Yi TIEN 1 2
  1. Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, TAIWAN, Taiwan
  2. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan City, TAIWAN, Taiwan

Group A streptococcus (GAS) is an important human pathogen that causes life-threatening invasive diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome (STSS). Angiopoietin-1 (Ang-1) promotes stabilization and maturation of new blood vessels, whereas angiopoietin-2 (Ang-2) can either promote VEGF-induced angiogenesis or destabilize blood vessels, causing endothelial apoptosis and leakiness in a context-dependent fashion. We hypothesized that Ang-1 and Ang-2 may regulate endothelial cell activation of GAS infection. Our data showed that in patients with invasive GAS infections, NF and STSS, the Ang-2 was increased at acute phase in contrast to Ang-1 which was decrease. These clinical results suggested that the differential regulation of Ang-1 and Ang-2 during severe GAS infection. To further elucidate the role of angiopoietins in the pathogenesis of severe GAS infection. First, angiopoietin dysregulations detected in GAS-infected cells were explored by RT-PCR and western blotting. In addition, a significant amount of Ang-2 is presynthesized and stored in the endothelial cell-specific organelles Weibel-Palade bodies (WPBs) under normal conditions and is rapidly released upon stimulation with various factors, such as thrombin and histamine. We next stimulated HUVECs with GAS and measured the levels of released Ang-2 by western blotting. These results suggested that GAS induced rapid Ang-2 release from endothelial cells. By transwell permeability assay, we observed that GAS induces endothelial hyperpermeability in HUVEC. Our studies implied that the vascular leakage was specifically induced by the differential regulation of Ang-1 and Ang-2 in severe GAS infections.