Abstract
Complement receptor 2-deficient (Cr2(-/-)) mice are resistant to mesenteric ischemia/reperfusion (I/R) injury because they lack a component of the natural Ab repertoire. Neither the nature of the Abs that are involved in I/R injury nor the composition of the target Ag, to which recognition is lacking in Cr2(-/-) mice, is known. Because anti-phospholipid Abs have been shown to mediate fetal growth retardation and loss when injected into pregnant mice, we performed experiments to determine whether anti-phospholipid Abs can also reconstitute I/R injury and, therefore, represent members of the injury-inducing repertoire that is missing in Cr2(-/-) mice. We demonstrate that both murine and human monoclonal and polyclonal Abs against negatively charged phospholipids can reconstitute mesenteric I/R-induced intestinal and lung tissue damage in Cr2(-/-) mice. In addition, Abs against beta2 glycoprotein I restore local and remote tissue damage in the Cr2(-/-) mice. Unlike Cr2(-/-) mice, reconstitution of I/R tissue damage in the injury-resistant Rag-1(-/-) mouse required the infusion of both anti-beta2-glycoprotein I and anti-phospholipid Ab. We conclude that anti-phospholipid Abs can bind to tissues subjected to I/R insult and mediate tissue damage.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Anticardiolipin / administration & dosage
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Antibodies, Anticardiolipin / therapeutic use
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Antibodies, Antiphospholipid / administration & dosage
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Antibodies, Antiphospholipid / metabolism
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Antibodies, Antiphospholipid / therapeutic use*
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / metabolism
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Antibodies, Monoclonal / therapeutic use
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Female
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Glycoproteins / immunology
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Glycoproteins / metabolism
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Homeodomain Proteins / genetics
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Humans
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Immune Sera / administration & dosage
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Infusions, Intravenous
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Intestinal Mucosa / blood supply*
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / pathology
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Lung / immunology
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Lung / pathology
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Male
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Mesenteric Arteries*
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Mice
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Mice, Knockout
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Receptors, Complement 3b / deficiency*
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Receptors, Complement 3b / genetics
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Receptors, Complement 3b / physiology
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Receptors, Complement 3d / deficiency*
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Receptors, Complement 3d / genetics
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Receptors, Complement 3d / physiology
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Reperfusion Injury / genetics
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Reperfusion Injury / immunology*
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Reperfusion Injury / prevention & control*
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beta 2-Glycoprotein I
Substances
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Antibodies, Anticardiolipin
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Antibodies, Antiphospholipid
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Antibodies, Monoclonal
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Glycoproteins
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Homeodomain Proteins
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Immune Sera
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Receptors, Complement 3b
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Receptors, Complement 3d
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beta 2-Glycoprotein I
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RAG-1 protein