Proteomics

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


ABSTRACT: 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.

SUBMITTER: Richard J Quigg   Chantal Moratz  Gregg Silverman  Gregg J Silverman  Liudmilla Kulik  Aleksey Novikov  V M Holers  George C Tsokos  Adam Markaryan  Jason W Reuter  Kuan Chen  Kathy A Andrews  Sherry D Fleming 

PROVIDER: E-GEOD-14862 | ArrayExpress | 2010-05-05

SECONDARY ACCESSION(S): GSE14862PRJNA112027

REPOSITORIES: GEO, ArrayExpress

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Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia-reperfusion injury.

Kulik Liudmila L   Fleming Sherry D SD   Moratz Chantal C   Reuter Jason W JW   Novikov Aleksey A   Chen Kuan K   Andrews Kathy A KA   Markaryan Adam A   Quigg Richard J RJ   Silverman Gregg J GJ   Tsokos George C GC   Holers V Michael VM  

Journal of immunology (Baltimore, Md. : 1950) 20090501 9


Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM Abs 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 mAb  ...[more]

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