Platelet thrombus formation in eHUS is prevented by anti-MBL2

摘要: E. coli associated Hemolytic Uremic Syndrome (epidemic hemolytic uremic syndrome, eHUS) caused by Shiga toxin-producing bacteria is characterized thrombocytopenia, microangiopathic anemia, and acute kidney injury that cause renal failure in up to 65% of affected patients. We hypothesized the mannose-binding lectin (MBL) pathway complement activation plays an important role human eHUS, as we previously demonstrated injection Toxin-2 (Stx-2) led fibrin deposition mouse glomeruli was blocked co-injection anti-MBL-2 antibody 3F8. However, markers platelet thrombosis were not delineated. To investigate effect 3F8 on thrombosis, used sections from our model (MBL-2+/+ Mbl-A/C-/-; MBL2 KI mouse). Mice control group received PBS, while mice a second Stx-2, those third Stx-2. Using double immunofluorescence (IF) followed digital image analysis, stained for fibrin(ogen) CD41 (marker platelets), von-Willebrand factor endothelial cells podocin podocytes). Electron microscopy (EM) performed ultrathin with HUS. Injection Stx-2 resulted increase both platelets glomeruli, administration reduced levels. EM studies confirmed CD41-positive objects observed IF platelets. The increases number levels are consistent generation platelet-fibrin thrombi prevented