Pathogenic Natural Antibodies Recognizing Annexin IV Are Required to Develop Intestinal Ischemia-Reperfusion Injury1

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 (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. mAb B4 was found to specifically recognize mouse annexin IV. Preinjection of recombinant annexin IV blocked IR injury in wild-type C57BL/6 mice, demonstrating the requirement for recognition of this protein to develop IR injury in the context of a complex natural Ab repertoire. Humans were also found to exhibit IgM natural Abs that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target Ag that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury.

[1]  K. Atabay,et al.  Impact of gradual blood flow increase on ischaemia-reperfusion injury in the rat cremaster microcirculation model. , 2008, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[2]  W. Robinson,et al.  Complement receptor CR2/CR1 deficiency protects mice from collagen-induced arthritis and associates with reduced autoantibodies to type II collagen and citrullinated antigens. , 2008, Molecular immunology.

[3]  Matthias M. Müller,et al.  Annexin A4 binding to anionic phospholipid vesicles modulated by pH and calcium , 2007, European Biophysics Journal.

[4]  A. Khamlichi,et al.  Internalization and molecular interactions of human CD21 receptor. , 2007, Molecular immunology.

[5]  J. Brooks,et al.  Angiostatin receptor annexin II in vascular tumors including angiosarcoma. , 2007, Human pathology.

[6]  Rodney K. Chan,et al.  The Differing Roles of the Classical and Mannose-Binding Lectin Complement Pathways in the Events following Skeletal Muscle Ischemia-Reperfusion1 , 2006, The Journal of Immunology.

[7]  R. Hardy.  B-1 B cells: development, selection, natural autoantibody and leukemia. , 2006, Current opinion in immunology.

[8]  J. Mocco,et al.  Alterations in plasma complement levels after human ischemic stroke. , 2006, Neurosurgery.

[9]  C. Schultz,et al.  Annexin A4 self-association modulates general membrane protein mobility in living cells. , 2006, Molecular biology of the cell.

[10]  M. Entman,et al.  The role of natural IgM in myocardial ischemia-reperfusion injury. , 2006, Journal of molecular and cellular cardiology.

[11]  J. Zweier,et al.  The role of oxidants and free radicals in reperfusion injury. , 2006, Cardiovascular research.

[12]  J. Mocco,et al.  Temporal pattern of C1q deposition after transient focal cerebral ischemia , 2006, Journal of neuroscience research.

[13]  A. Waheed,et al.  Proteomic characterization of lipid rafts markers from the rat intestinal brush border. , 2006, Biochemical and Biophysical Research Communications - BBRC.

[14]  Rodney K. Chan,et al.  Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid peptides that bind to pathogenic IgM. , 2006, Surgery.

[15]  Ralph Weissleder,et al.  Identification of the target self-antigens in reperfusion injury , 2006, The Journal of experimental medicine.

[16]  H. Mochizuki,et al.  Gut ischemia-reperfusion affects gut mucosal immunity: A possible mechanism for infectious complications after severe surgical insults* , 2006, Critical care medicine.

[17]  Wei-Hwa Lee,et al.  Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure. , 2005, Kidney international.

[18]  J. Vinten-johansen,et al.  Myocardial protection in reperfusion with postconditioning , 2005, Expert review of cardiovascular therapy.

[19]  S. Moss,et al.  Annexins: linking Ca2+ signalling to membrane dynamics , 2005, Nature Reviews Molecular Cell Biology.

[20]  V. Holers,et al.  Coligation of the B Cell Receptor with Complement Receptor Type 2 (CR2/CD21) Using Its Natural Ligand C3dg: Activation without Engagement of an Inhibitory Signaling Pathway1 , 2005, The Journal of Immunology.

[21]  G. Silverman,et al.  Natural antibodies and the autoimmunity of atherosclerosis , 2005, Springer Seminars in Immunopathology.

[22]  L. Herzenberg,et al.  Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion , 2005, Springer Seminars in Immunopathology.

[23]  J. Iglesias,et al.  Evolutionary perspective on annexin calcium-binding domains. , 2004, Biochimica et biophysica acta.

[24]  Ryan P. Egan,et al.  Anti-Phospholipid Antibodies Restore Mesenteric Ischemia/Reperfusion-Induced Injury in Complement Receptor 2/Complement Receptor 1-Deficient Mice1 , 2004, The Journal of Immunology.

[25]  L. Matrisian,et al.  Annexins expressed on the cell surface serve as receptors for adhesion to immobilized fetuin-A. , 2004, Biochimica et biophysica acta.

[26]  S. Moss,et al.  Annexin–Actin Interactions , 2004, Traffic.

[27]  Volker Gerke,et al.  Annexins – unique membrane binding proteins with diverse functions , 2004, Journal of Cell Science.

[28]  C. Scharf,et al.  Increased expression and altered location of annexin IV in renal clear cell carcinoma: a possible role in tumour dissemination. , 2004, Cancer letters.

[29]  A. Novick,et al.  Differential protein profiling in renal‐cell carcinoma , 2004, Molecular carcinogenesis.

[30]  H. Daniel,et al.  Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis , 2004, International journal of cancer.

[31]  H. Hechtman,et al.  Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Jun Yan,et al.  Identification of a novel protein complex containing annexin A4, rabphilin and synaptotagmin , 2004, FEBS letters.

[33]  E. Lapointe,et al.  Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin , 2004, Arthritis research & therapy.

[34]  H. Ohdan,et al.  Peritoneal Cavity B Cells Are Precursors of Splenic IgM Natural Antibody-Producing Cells 1 , 2003, The Journal of Immunology.

[35]  M. Glocker,et al.  B cell activation leads to shedding of complement receptor type II (CR2/CD21) , 2003, European journal of immunology.

[36]  H. Ohkawa,et al.  Augmentation of ethanol-induced cell damage and activation of nuclear factor-kappa B by annexin IV in cultured cells. , 2003, Alcoholism, clinical and experimental research.

[37]  B. Kishore,et al.  Annexin A4 Reduces Water and Proton Permeability of Model Membranes but Does Not Alter Aquaporin 2–mediated Water Transport in Isolated Endosomes , 2003, The Journal of general physiology.

[38]  M. Perretti,et al.  Annexin 1: an endogenous anti-inflammatory protein. , 2003, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[39]  H Zhao,et al.  Role for the alternative complement pathway in ischemia/reperfusion injury. , 2003, The American journal of pathology.

[40]  T. Yamagaki,et al.  A Potential Endogenous Ligand of Annexin IV in the Exocrine Pancreas , 2002, The Journal of Biological Chemistry.

[41]  L. Kobzik,et al.  Functional Activity of Natural Antibody is Altered in Cr2-Deficient Mice1 , 2002, The Journal of Immunology.

[42]  J. Guthridge,et al.  Mice Deficient in Complement Receptors 1 and 2 Lack a Tissue Injury-Inducing Subset of the Natural Antibody Repertoire1 , 2002, The Journal of Immunology.

[43]  H. Ohkawa,et al.  Ethanol-induced augmentation of annexin IV expression in rat C6 glioma and human A549 adenocarcinoma cells. , 2002, Alcoholism, clinical and experimental research.

[44]  K. Massé,et al.  Annexin IV (Xanx-4) has a functional role in the formation of pronephric tubules. , 2002, Development.

[45]  Jiyun V Kim,et al.  Annexin II: a plasminogen-plasminogen activator co-receptor. , 2002, Frontiers in bioscience : a journal and virtual library.

[46]  V. M. Holers,et al.  Complement Inhibitor, Complement Receptor 1-Related Gene/Protein y-Ig Attenuates Intestinal Damage After the Onset of Mesenteric Ischemia/Reperfusion Injury in Mice1 , 2001, The Journal of Immunology.

[47]  Michael C. Montalto,et al.  Inhibition of Mannose-Binding Lectin Reduces Postischemic Myocardial Reperfusion Injury , 2001, Circulation.

[48]  H. Ohkawa,et al.  Alteration of annexin IV expression in alcoholics. , 2001, Alcoholism, clinical and experimental research.

[49]  J. Kearney,et al.  B1 cells: similarities and differences with other B cell subsets. , 2001, Current opinion in immunology.

[50]  E. Deitch.  Role of the gut lymphatic system in multiple organ failure , 2001, Current opinion in critical care.

[51]  J. Schölmerich,et al.  Apoptotic signaling during initiation of detachment-induced apoptosis ("anoikis") of primary human intestinal epithelial cells. , 2001, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[52]  Jianzhu Chen,et al.  B-1 and B-2 Cell–Derived Immunoglobulin M Antibodies Are Nonredundant Components of the Protective Response to Influenza Virus Infection , 2000, The Journal of experimental medicine.

[53]  G. Silverman,et al.  Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. , 2000, The Journal of clinical investigation.

[54]  L. Herzenberg.  B‐1 cells: the lineage question revisited , 2000, Immunological reviews.

[55]  J. Macfie,et al.  Gut origin of sepsis: a prospective study investigating associations between bacterial translocation, gastric microflora, and septic morbidity , 1999, Gut.

[56]  J. Silver,et al.  Positive selection of natural autoreactive B cells. , 1999, Science.

[57]  M. Weiser,et al.  Intestinal reperfusion injury is mediated by IgM and complement. , 1999, Journal of applied physiology.

[58]  B. Starnes,et al.  Antiinflammatory effects of soluble complement receptor type 1 promote rapid recovery of ischemia/reperfusion injury in rat small intestine. , 1999, Clinical immunology.

[59]  A. Levine,et al.  New isolation technique to study apoptosis in human intestinal epithelial cells. , 1998, American Journal of Pathology.

[60]  V. Holers,et al.  Expression of complement receptors 1 and 2 on follicular dendritic cells is necessary for the generation of a strong antigen-specific IgG response. , 1998, Journal of immunology.

[61]  N. Mayran,et al.  Polarized localizations of annexins I, II, VI and XIII in epithelial cells of intestinal, hepatic and pancreatic tissues. , 1998, Journal of cell science.

[62]  M. Sileghem,et al.  CD5+ B lymphocytes are the main source of antibodies reactive with non‐parasite antigens in Trypanosoma congolense‐infected cattle , 1997, Immunology.

[63]  N. Mayran,et al.  Cellular and subcellular localizations of annexins I, IV, and VI in lung epithelia. , 1996, The American journal of physiology.

[64]  C. Creutz,et al.  Ca(2+)-dependent binding of endonexin (annexin IV) to membranes: analysis of the effects of membrane lipid composition and development of a predictive model for the binding interaction. , 1994, Biochemistry.

[65]  D. Granger,et al.  Mechanisms of Reperfusion Injury , 1994, The American journal of the medical sciences.

[66]  C. Valeri,et al.  Neutrophil and Nonneutrophil‐Mediated Injury in Intestinal Ischemia‐Reperfusion , 1993, Annals of surgery.

[67]  V. Vetvicka,et al.  Microvascular effects of complement blockade with soluble recombinant CR1 on ischemia/reperfusion injury of skeletal muscle. , 1993, Journal of immunology.

[68]  L. Arnold,et al.  Restricted immunoglobulin variable region gene usage by normal Ly-1 (CD5+) B cells that recognize phosphatidyl choline , 1989, The Journal of experimental medicine.

[69]  L. McManus,et al.  Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury. , 1988, Circulation.

[70]  L. Arnold,et al.  Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidyl choline. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes , 1988, The Journal of experimental medicine.

[71]  M. Grisham,et al.  Role of neutrophils in ischemia-reperfusion-induced microvascular injury. , 1987, The American journal of physiology.

[72]  A. Larena-Avellaneda,et al.  Intestinal ischemia , 2011, International Journal of Colorectal Disease.

[73]  K. Monastyrskaya,et al.  Annexins sense changes in intracellular pH during hypoxia. , 2008, The Biochemical journal.

[74]  V. Holers,et al.  Complement receptor 2, natural antibodies and innate immunity: Inter-relationships in B cell selection and activation. , 2007, Molecular immunology.

[75]  Deborah A. Brown.  Structure and function of membrane rafts. , 2002, International journal of medical microbiology : IJMM.

[76]  G. Silverman,et al.  Neo-self antigens and the expansion of B-1 cells: lessons from atherosclerosis-prone mice. , 2000, Current topics in microbiology and immunology.

[77]  D. Fearon,et al.  The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. , 1995, Annual review of immunology.

[78]  A. Rigal,et al.  Cellular and subcellular localization of annexin IV in rabbit intestinal epithelium, pancreas and liver , 1991, Biology of the cell.