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E-GEOD-14862 - Pathogenic Natural Antibodies Recognizing Annexin IV Are Required to Develop Intestinal Ischemia-Reperfusion Injury

Status
Submitted on 17 February 2009, released on 5 May 2010, last updated on 27 March 2012
Organism
Mus musculus, unidentified
Samples (4)
Array (1)
Protocols (7)
Description
Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1-/- mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. Keywords: Natural antibodies, Annexin, Ischemia Reperfusion, Inflammation, Complement In the study presented here, a total of 4 custom spotted antigen slides were hybridized with known antibodies.
Experiment type
proteomic profiling by array 
Contacts
Gregg Silverman <gsilverman@ucsd.edu>, Adam Markaryan, Aleksey Novikov, Chantal Moratz, George C Tsokos, Gregg J Silverman, Jason W Reuter, Kathy A Andrews, Kuan Chen, Liudmilla Kulik, Richard J Quigg, Sherry D Fleming, V M Holers
Citation
Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia-reperfusion injury. Kulik L, Fleming SD, Moratz C, Reuter JW, Novikov A, Chen K, Andrews KA, Markaryan A, Quigg RJ, Silverman GJ, Tsokos GC, Holers VM.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-14862.idf.txt
Sample and data relationshipE-GEOD-14862.sdrf.txt
Raw data (1)E-GEOD-14862.raw.1.zip
Processed data (1)E-GEOD-14862.processed.1.zip
Array designA-GEOD-8165.adf.txt
R ExpressionSetE-GEOD-14862.eSet.r
Links