Human mannose-binding lectin inhibitor prevents Shiga toxin-induced renal injury.

Authors: Ozaki, M  Kang, Y  Tan, YS  Pavlov, VI  Liu, B  Boyle, DC  Kushak, RI  Skjoedt, MO  Grabowski, EF  Taira, Y  Stahl, GL 
Citation: Ozaki M, etal., Kidney Int. 2016 Jul 1. pii: S0085-2538(16)30202-2. doi: 10.1016/j.kint.2016.05.011.
Pubmed: (View Article at PubMed) PMID:27378476
DOI: Full-text: DOI:10.1016/j.kint.2016.05.011

Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC HUS) is a worldwide endemic problem, and its pathophysiology is not fully elucidated. Here we tested whether the mannose-binding lectin (MBL2), an initiating factor of lectin complement pathway activation, plays a crucial role in STEC HUS. Using novel human MBL2-expressing mice (MBL2 KI) that lack murine Mbls (MBL2+/+Mbl1-/-Mbl2-/-), a novel STEC HUS model consisted of an intraperitoneal injection with Shiga toxin-2 (Stx-2) with or without anti-MBL2 antibody (3F8, intraperitoneal). Stx-2 induced weight loss, anemia, and thrombocytopenia and increased serum creatinine, free serum hemoglobin, and cystatin C levels, but a significantly decreased glomerular filtration rate compared with control/sham mice. Immunohistochemical staining revealed renal C3d deposition and fibrin deposition in glomeruli in Stx-2-injected mice. Treatment with 3F8 completely inhibited serum MBL2 levels and significantly attenuated Stx-2 induced-renal injury, free serum hemoglobin levels, renal C3d, and fibrin deposition and preserved the glomerular filtration rate. Thus, MBL2 inhibition significantly protected against complement activation and renal injury induced by Stx-2. This novel mouse model can be used to study the role of complement, particularly lectin pathway-mediated complement activation, in Stx-2-induced renal injury.

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CRRD Object Information
CRRD ID: 11530050
Created: 2016-08-23
Species: All species
Last Modified: 2016-08-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.