Naturally Occurring Autoantibodies Mediate Ischemia/Reperfusion-Induced Tissue Injury

  • Sherry D. Fleming
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 750)


Ischemia and reperfusion events within the heart and brain and similar trauma-induced ischemia/reperfusion events lead to significant morbidity and mortality. In the past two decades, an excessive innate immune response has been identified as the mediator of reperfusion-induced tissue damage. Recent evidence indicates that naturally occurring autoantibody (NAb) activation of complement is a major mechanism of injury due to ischemia/reperfusion. This chapter focuses on the antigens exposed by ischemia and recognized by NAbs, the mechanism of complement activation by damaging NAbs and the protective role of IVIG in ischemia/reperfusion-induced pathology.


Complement Activation Mannose Binding Lectin Membrane Attack Complex Natural Antibody Lectin Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Annunziato L, Pignataro G, Boscia F et al. ncx1, ncx2, and ncx3 gene product expression and function in neuronal anoxia and brain ischemia. AnnN Y Acad Sci 2007; 1099:413–26. PMID: 17446481 doi: 10.1196/annals. 1387.050CrossRefGoogle Scholar
  2. 2.
    Kaljusto ML, Rutkovsky A, Stenslokken KO et al. Postconditioning in mouse hearts is inhibited by blocking the reverse mode of the sodium-calcium exchanger. Interact Cardiovasc Thorac Surg 2010; 10:743–8. PMID:20139199 doi:10.1510/icvts.2009.217083PubMedCrossRefGoogle Scholar
  3. 3.
    Nizet V, Johnson RS. Interdependence of hypoxic and innate immune responses. Nat Rev Immunol 2009; 9:609–17. PMID: 19704417 doi:10.1038/nri2607PubMedCrossRefGoogle Scholar
  4. 4.
    Taylor CT, Cummins EP. The role of NF-kappaB in hypoxia-induced gene expression. Ann N Y Acad Sci 2009; 1177:178–84. PMID:19845620 doi: 10.1111/j.l749-6632.2009.05024.xPubMedCrossRefGoogle Scholar
  5. 5.
    Zhao ZQ. Oxidative stress-elicited myocardial apoptosis during reperfusion. Curr Opin Pharmacol 2004; 4:159–65. PMID:15063360 doi: 10.1016/j.coph.2003.10.010PubMedCrossRefGoogle Scholar
  6. 6.
    Shea-Donohue T, Anderson J, Swiecki C. Ischemia/reperfusion injury. In: Tsokos GC, Atkins JL, eds. Combat Medicine. Totowa, New Jersey: Humana Press; 2003:219–248.CrossRefGoogle Scholar
  7. 7.
    Hernandez LA, Grisham MB, Twohig B et al. Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am J Physiol 1987; 253:H699–703. PMID:3631303PubMedGoogle Scholar
  8. 8.
    Sisley AC, Desai T, Harig JM et al. Neutrophil depletion attenuates human intestinal reperfusion injury. J Surg Res 1994; 57:192–6. PMID:8041137 doi: 10.1006/jsre. 1994.1130PubMedCrossRefGoogle Scholar
  9. 9.
    Abonia JP, Friend DS, Austen WG Jr. et al. Mast cell protease 5 mediates ischemia-reperfusion injury of mouse skeletal muscle. J Immunol 2005; 174:7285–91. PMID: 15905575PubMedGoogle Scholar
  10. 10.
    Arumugam TV, Magnus T, Woodruff TM et al. Complement mediators in ischemia-reperfusion injury. Clin Chim Acta 2006; 374:33–45. PMID:16872589 doi:10.1016/j.cca.2006.06.010PubMedCrossRefGoogle Scholar
  11. 11.
    Kim SJ, Gershov D, Ma X et al. I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation. J Exp Med 2002; 196:655–65. PMID: 12208880 doi:10.1084/jem.20020542PubMedCrossRefGoogle Scholar
  12. 12.
    Baumgarth N, Herman OC, Jager GC et al. B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J Exp Med 2000; 192:271–80. PMID:10899913 doi: 10.1084/jem. 192.2.271PubMedCrossRefGoogle Scholar
  13. 13.
    Boes M. Role of natural and immune IgM antibodies in immune responses. Mol Immunol 2000; 37:1141–9. PMID:11451419 doi:10.1016/S0161-5890(01)00025-6PubMedCrossRefGoogle Scholar
  14. 14.
    Avrameas S. Natural autoantibodies: from ‘horror autotoxicus’ to ‘gnothi seauton’. Immunol Today 1991; 12:154–9. PMID:1715166PubMedGoogle Scholar
  15. 15.
    Avrameas S, Ternynck T. Natural autoantibodies: the other side of the immune system. Res Immunol 1995; 146:235–48. PMID:8577986 doi: 10.1016/0923-2494(96)80259-8PubMedCrossRefGoogle Scholar
  16. 16.
    Weiser MR, Williams JP, Moore FD et al. Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement. J Exp Med 1996; 183:2343–8. PMID:8642343 doi:10.1084/jem.l83.5.2343PubMedCrossRefGoogle Scholar
  17. 17.
    Williams JP, Pechet TT, Weiser MR et al. Intestinal reperfusion injury is mediated by IgM and complement. J Appl Physiol 1999; 86:938–42. PMID:10066708PubMedGoogle Scholar
  18. 18.
    Zhang M, Michael LH, Grosjean SA et al. The role of natural IgM in myocardial ischemia-reperfusion injury. J Mol Cell Cardiol 2006; 41:62–7. PMID: 16781728 doi:10.1016/j.yjmcc.2006.02.006PubMedCrossRefGoogle Scholar
  19. 19.
    Park P, Haas M, Cunningham PN et al. Injury in renal ischemia-reperfusion is independent from immunoglobulins and T-lymphocytes. Am J Physiol Renal Physiol 2002; 282:F352–7. PMID: 11788450PubMedGoogle Scholar
  20. 20.
    Renner B, Strassheim D, Amura CR et al. B-cell subsets contribute to renal injury and renal protection after ischemia/reperfusion. J Immunol 2010; 185:4393–400. PMID:20810984 doi: 10.4049/jimmunol.0903239PubMedCrossRefGoogle Scholar
  21. 21.
    Holers VM, Kulik L. Complement receptor 2, natural antibodies and innate immunity: Inter-relationships in B-cell selection and activation. Mol Immunol 2007; 44:64–72. PMID: 16876864 doi: 10.1016/j. molimm.2006.07.003PubMedCrossRefGoogle Scholar
  22. 22.
    Ochsenbein AF, Zinkernagel RM. Natural antibodies and complement link innate and acquired immunity. Immunol Today 2000; 21:624–30. PMID:11114423 doi:10.1016/S0167-5699(00)01754-0PubMedCrossRefGoogle Scholar
  23. 23.
    Fleming SD, Shea-Donohue T, Guthridge JM et al. Mice deficient in complement receptors 1 and 2 lack a tissue injury-inducing subset of the natural antibody repertoire. J Immunol 2002; 169:2126–33. PMID: 12165541PubMedGoogle Scholar
  24. 24.
    Reid RR, Woodcock S, Shimabukuro-Vornhagen A et al. Functional activity of natural antibody is altered in Cr2-deficient mice. J Immunol 2002; 169:5433–5440. PMID: 12421918PubMedGoogle Scholar
  25. 25.
    Woods KM, Pope MR, Hoffman SM et al. CR2+ Marginal zone B-cell production of pathogenic natural antibodies is C3 independent. J Immunol 2011.Google Scholar
  26. 26.
    Fleming SD, Monestier M, Tsokos GC. Accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice. J Immunol 2004; 173:4230–5. PMID: 15356174PubMedGoogle Scholar
  27. 27.
    Williams JP, Pechet TTV, Weiser MR et al. Intestinal reperfusion injury is mediated by IgM and complement. J Appl Physiol 1999; 86:938–42. PMID:10066708PubMedGoogle Scholar
  28. 28.
    Zhang M, Austen WG, Chiu I et al. Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury. Proc Natl Acad Sci USA 2004; 101:3886–91. PMID:14999103 doi:10.1073/pnas.0400347101PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang M, Alicot EM, Chiu I et al. Identification of the target self-antigens in reperfusion injury. J Exp Med 2006; 203:141–52. PMID: 16390934 doi:10.1084/jem.20050390PubMedCrossRefGoogle Scholar
  30. 30.
    Chan RK, Verna N, Afnan J et al. Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid peptides that bind to pathogenic IgM. Surgery 2006; 139:236–43. PMID: 16455333 doi:10.1016/j.surg.2005.05.028PubMedCrossRefGoogle Scholar
  31. 31.
    Haas MS, Alicot EM, Schuerpf F et al. Blockade of self-reactive IgM significantly reduces injury in a murine model of acute myocardial infarction. Cardiovasc Res 2010; 87:618–27. PMID:20462867 doi:10.1093/cvr/cvq141PubMedCrossRefGoogle Scholar
  32. 32.
    Kulik L, Fleming SD, Moratz C et al. Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia-reperfusion injury. J Immunol 2009; 182:5363–73. PMID:19380783 doi: 10.4049/jimmunol.0803980PubMedCrossRefGoogle Scholar
  33. 33.
    Friedman P, Horkko S, Steinberg D et al. Correlation of antiphospholipid antibody recognition with the structure of synthetic oxidized phospholipids. Importance of Schiff base formation and aldol condensation. J Biol Chem 2002; 277:7010–20. PMID: 11744722 doi: 10.1074/jbc.Ml08860200PubMedCrossRefGoogle Scholar
  34. 34.
    Sparkes BL, Slone EE, Roth M et al. Intestinal lipid alterations occur prior to antibody-induced prostaglandin E2 production in a mouse model of ischemia/reperfusion. Biochim Biophys Acta 2010; 1801:517–525.PubMedCrossRefGoogle Scholar
  35. 35.
    Fleming SD, Egan RP, Chai C et al. Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice. J Immunol 2004; 173:7055–61. PMID: 15557203PubMedGoogle Scholar
  36. 36.
    Monestier M, Kandiah DA, Kouts S et al. Monoclonal antibodies from NZW x BXSB F1 mice to beta2 glycoprotein I and cardiolipin. Species specificity and charge-dependent binding. J Immunol 1996; 156:2631–41. PMID:8786329PubMedGoogle Scholar
  37. 37.
    Fleming SD, Pope MR, Hoffman SM et al. Domain V peptides inhibit beta2-glycoprotein I-mediated mesenteric ischemia/reperfusion-inducedtissue damage and inflammation. J Immunol 2010; 185:6168–78. PMID:20956350 doi:10.4049/jimmunol.l002520PubMedCrossRefGoogle Scholar
  38. 38.
    Hörkkö S, Miller E, Dudl E et al. Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein. J Clin Invest 1996; 98:815–25. PMID:8698874 doi: 10.1172/JCI118854PubMedCrossRefGoogle Scholar
  39. 39.
    Witztum JL, Horkko S. The role of oxidized LDL in atherogenesis: immunological response and anti-phospholipid antibodies. Ann NY Acad Sci 1997; 811:88–96; discussion 96-89.PubMedCrossRefGoogle Scholar
  40. 40.
    Sjöberg BG, Su J, Dahlbom I et al. Low levels of IgM antibodies against phosphorylcholine-A potential risk marker for ischemic stroke in men. Atherosclerosis 2009; 203:528–32. PMID: 18809177 doi: 10.1016/j. atherosclerosis.2008.07.009PubMedCrossRefGoogle Scholar
  41. 41.
    Keith MP, Moratz C, Egan R et al. Anti-ribonucleoprotein antibodies mediate enhanced lung injury following mesenteric ischemia/reperfusion in Rag-1(-/-) mice. Autoimmunity 2007; 40:208–16. PMID: 17453720 doi: 10.1080/08916930701262986PubMedCrossRefGoogle Scholar
  42. 42.
    Zschörnig O, Opitz F, Muller M. Annexin A4 binding to anionic phospholipid vesicles modulated by pH and calcium. Eur Biophys J 2007; 36:415–24. PMID:17440717 doi:10.1007/s00249-007-0147-1PubMedCrossRefGoogle Scholar
  43. 43.
    Balasubramanian K, Maiti SN, Schroit AJ. Recruitment of beta-2-glycoprotein 1 to cell surfaces in extrinsic and intrinsic apoptosis. Apoptosis 2005; 10:439–46. PMID:15843904 doi:10.1007/sl0495-005-0817-3PubMedCrossRefGoogle Scholar
  44. 44.
    Murakami N, Elzinga M, Singh SS et al. Direct binding of myosin II to phospholipid vesicles via tail regions and phosphorylation of the heavy chains by protein kinase C. J Biol Chem 1994; 269:16082–90. PMID:8206908PubMedGoogle Scholar
  45. 45.
    Kato M, Fukuda H, Nonaka T et al. Cleavage of nonmuscle myosin heavy chain-A during apoptosis in human Jurkat T-cells. J Biochem 2005; 137:157–66. PMID:15749830 doi:10.1093/jb/mvi015PubMedCrossRefGoogle Scholar
  46. 46.
    Hill JH, Ward PA. The phlogistic role of C3 leukotactic fragments in myocardial infarcts of rats. J Exp Med 1971; 133:885–900. PMID:4993831 doi:10.1084/jem.l33.4.885PubMedCrossRefGoogle Scholar
  47. 47.
    Gorsuch WB, Guikema BJ, Fritzinger DC et al. Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury. Mol Immunol 2009; 47:506–10. PMID:19747734 doi: 10.1016/j. molimm.2009.08.017PubMedCrossRefGoogle Scholar
  48. 48.
    Hart ML, Ceonzo KA, Shaffer LA et al. Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q. J Immunol 2005; 174:6373–80. PMID: 15879138PubMedGoogle Scholar
  49. 49.
    Zhang M, Takahashi K, Alicot EM et al. Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury. J Immunol 2006; 177:4727–34. PMID: 16982912PubMedGoogle Scholar
  50. 50.
    Chan RK, Ibrahim SI, Takahashi K et al. The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion. J Immunol 2006; 177:8080–5. PMID: 17114482PubMedGoogle Scholar
  51. 51.
    Zhou W, Farrar CA, Abe K et al. Predominant role for C5b-9 in renal ischemia/reperfusion injury. J Clin Invest 2000; 105:1363–71. PMID:10811844 doi:10.1172/JCI8621PubMedCrossRefGoogle Scholar
  52. 52.
    Hill J, Lindsay TF, Ortiz F et al. Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat. J Immunol 1992; 149:1723–8. PMID: 1387151PubMedGoogle Scholar
  53. 53.
    Davis WD, Brey RL. Antiphospholipid antibodies and complement activation in patients with cerebral ischemia. Clin Exp Rheumatol 1992; 10:455–60. PMID:1458697PubMedGoogle Scholar
  54. 54.
    Pemberton M, Anderson G, Vetvicka V et al. Microvascular effects of complement blockade with soluble recombinant CRI on ischemia/reperfusion injury of skeletal muscle. J Immunol 1993; 150:5104–13. PMID:8496606PubMedGoogle Scholar
  55. 55.
    Buerke M, Murohara T, Lefer AM. Cardioprotective effects of aC1 esterase inhibitor in myocardial ischemia and reperfusion. Circulation 1995; 91:393–402. PMID:7805243PubMedCrossRefGoogle Scholar
  56. 56.
    Horstick G, Heimann A, Gotze O et al. Intracoronary application of C1 esterase inhibitor improves cardiac function and reduces myocardial necrosis in an experimental model of ischemia and reperfusion. Circulation 1997; 95:701–8. PMID:9024160PubMedCrossRefGoogle Scholar
  57. 57.
    Karpel-Massler G, Fleming SD, Kirschfink M et al. Human Cl esterase inhibitor attenuates murine mesenteric ischemia/reperfusion induced local organ injury. JSurg Res 2003; 115:247–56. PMID: 14697291 doi:10.1016/S0022-4804(03)00192-6CrossRefGoogle Scholar
  58. 58.
    Nielsen EW, Mollnes TE, Harlan JM et al. C1-inhibitor reduces the ischaemia-reperfusion injury of skeletal muscles in mice after aortic cross-clamping. Scand J Immunol 2002; 56:588–92. PMID: 12472670 doi: 10.1046/j. 1365-3083.2002.01173.xPubMedCrossRefGoogle Scholar
  59. 59.
    Akita N, Nakase H, Kaido T et al. Protective effect of C1 esterase inhibitor on reperfusion injury in the rat middle cerebral artery occlusion model. Neurosurgery 2003; 52:395–400; discussion 400-391.PubMedCrossRefGoogle Scholar
  60. 60.
    Storini C, Rossi E, Marrella V et al. C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation. Neurobiol Dis 2005; 19:10–7. PMID: 15837556 doi:10.1016/j.nbd.2004.11.001PubMedCrossRefGoogle Scholar
  61. 61.
    Matsushita M, Thiel S, Jensenius JC et al. Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol 2000; 165:2637–42. PMID: 10946292PubMedGoogle Scholar
  62. 62.
    Nielsen EW, Waage C, Fure H et al. Effect of supraphysiologic levels of C1-inhibitor on the classical, lectin and alternative pathways of complement. Mol Immunol 2007; 44:1819–26. PMID: 17101176 doi: 10.1016/j.molimm.2006.10.003PubMedCrossRefGoogle Scholar
  63. 63.
    De Simoni MG, Storini C, Barba M et al. Neuroprotection by complement (C1) inhibitor in mouse transient brain ischemia. J Cereb Blood Flow Metab 2003; 23:232–9. PMID: 12571454 doi: 10.1097/00004647-200302000-00010PubMedCrossRefGoogle Scholar
  64. 64.
    Walsh MC, Bourcier T, Takahashi K et al. Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J Immunol 2005; 175:541–6. PMID: 15972690PubMedGoogle Scholar
  65. 65.
    Moller-Kristensen M, Wang W, Ruseva M et al. Mannan-binding lectin recognizes structures on ischaemic reperfused mouse kidneys and is implicated in tissue injury. Scand J Immunol 2005; 61:426–34. PMID:15882434 doi:10.1111/j.l365-3083.2005.01591.xPubMedCrossRefGoogle Scholar
  66. 66.
    Arnold JN, Wormald MR, Suter DM et al. Human serum IgM glycosylation; identification of glycoforms that can bind to mannan-binding lectin. J Biol Chem 2005; 280:29080–7. PMID: 15955802 doi: 10.1074/jbc.M504528200PubMedCrossRefGoogle Scholar
  67. 67.
    Roos A, Bouwman LH, Munoz J et al. Functional characterization of the lectin pathway of complement in human serum. Mol Immunol 2003; 39:655–68. PMID: 12493641 doi:10.1016/S0161-5890(02)00254-7PubMedCrossRefGoogle Scholar
  68. 68.
    Busche MN, Pavlov V, Takahashi K et al. Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin. Am J Physiol Heart Circ Physiol 2009; 297:H1853–9. PMID: 19749170 doi: 10.1152/ajpheart.00049.2009PubMedCrossRefGoogle Scholar
  69. 69.
    Bilgin YM, Brand A, Berger SP et al. Mannose-binding lectin is involved in multiple organ dysfunction syndrome after cardiac surgery: effects of blood transfusions. Transfusion 2008; 48:601–8. PMID: 18194386 doi: 10.1111/j. 1537-2995.2007.01585.XPubMedCrossRefGoogle Scholar
  70. 70.
    Berger SP, Daha MR. Emerging role of the mannose-binding lectin-dependent pathway of complement activation in clinical organ transplantation. Curr Opin Organ Transplant 2010.Google Scholar
  71. 71.
    Huang Y, Qiao F, Atkinson C et al. A novel targeted inhibitor of the alternative pathway of complement and its therapeutic application in ischemia/reperfusion injury. J Immunol 2008; 181:8068–76. PMID: 19017999PubMedGoogle Scholar
  72. 72.
    Atkinson C, Song H, Lu B et al. Targeted complement inhibition by C3 d recognition ameliorates tissue injury without apparent increase in susceptibility to infection. J Clin Invest 2005; 115:2444–53. PMID: 16127466 doi:10.1172/JCI25208PubMedCrossRefGoogle Scholar
  73. 73.
    Zhang M, Carroll MC. Natural antibody mediated innate autoimmune response. Mol Immunol 2007; 44:103–10. PMID: 16876247 doi:10.1016/j.molimm.2006.06.022PubMedCrossRefGoogle Scholar
  74. 74.
    Lee H, Green DJ, Lai L et al. Early complement factors in the local tissue immunocomplex generated during intestinal ischemia/reperfusion injury. Mol Immunol 2010; 47:972–81. PMID:20004473 doi: 10.1016/j. molimm.2009.11.022PubMedCrossRefGoogle Scholar
  75. 75.
    Vani J, Elluru S, Negi VS et al. Role of natural antibodies in immune homeostasis: IVIg perspective. Autoimmun Rev 2008; 7:440–4. PMID:18558359 doi:10.1016/j.autrev.2008.04.011PubMedCrossRefGoogle Scholar
  76. 76.
    Basta M. Modulation of complement-mediated immune damage by intravenous immune globulin. Clin Exp Immunol 1996; 104(Suppl l):21–5. PMID:8625538PubMedGoogle Scholar
  77. 77.
    Basta M, Dalakas MC. High-dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments. J Clin Invest 1994; 94:1729–35. PMID:7962520 doi: 10.1172/JCI117520PubMedCrossRefGoogle Scholar
  78. 78.
    Lutz HU, Stammler P, Jelezarova E et al. High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn-IgG complexes. Blood 1996; 88:184–93. PMID:8704173PubMedGoogle Scholar
  79. 79.
    Lutz HU, Stammler P, Bianchi V et al. Intravenously applied IgG stimulates complement attenuation in a complement-dependent autoimmune disease at the amplifying C3 convertase level. Blood 2004; 103:465–72. PMID:14512320 doi: 10.1182/blood-2003-05-1530PubMedCrossRefGoogle Scholar
  80. 80.
    Raju R, Dalakas MC. Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes. Brain 2005; 128:1887–96. PMID:15857930 doi:10.1093/brain/awh518PubMedCrossRefGoogle Scholar
  81. 81.
    Basta M, Van Goor F, Luccioli S et al. F(ab’)2-mediated neutralization of C3a and C5a anaphylotoxins: a novel effectorfunctionofimmunoglobulins. Nat Med 2003; 9:431–8. PMID:12612546 doi:10.1038/nm836PubMedCrossRefGoogle Scholar
  82. 82.
    Anderson J, Fleming SD, Rehrig S et al. Intravenous immunoglobulin attenuates mesenteric ischemia-reperfusion injury. Clin Immunol 2005; 114:137–46. PMID:15639647 doi: 10.1016/j. clim.2004.08.018PubMedCrossRefGoogle Scholar
  83. 83.
    Arumugam TV, Tang SC, Lathia JD et al. Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proc Natl Acad Sci USA 2007; 104:14104–9. PMID:17715065 doi:10.1073/pnas.0700506104PubMedCrossRefGoogle Scholar
  84. 84.
    Arumugam TV, Okun E, Tang SC et al. Toll-like receptors in ischemia-reperfusion injury. Shock 2009; 32:4–16. PMID:19008778 doi:10.1097/SHK.0b013e318193e333PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Sherry D. Fleming
    • 1
  1. 1.Division of BiologyKansas State UniversityManhattanUSA

Personalised recommendations