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.
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Authors | Sherry D Fleming, Ryan P Egan, Chunyan Chai, Guillermina Girardi, V Michael Holers, Jane Salmon, Marc Monestier, George C Tsokos |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 173
Issue 11
Pg. 7055-61
(Dec 01 2004)
ISSN: 0022-1767 [Print] United States |
PMID | 15557203
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Anticardiolipin
- Antibodies, Antiphospholipid
- Antibodies, Monoclonal
- Glycoproteins
- Homeodomain Proteins
- Immune Sera
- Receptors, Complement 3b
- Receptors, Complement 3d
- beta 2-Glycoprotein I
- RAG-1 protein
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Topics |
- Animals
- Antibodies, Anticardiolipin
(administration & dosage, therapeutic use)
- Antibodies, Antiphospholipid
(administration & dosage, metabolism, therapeutic use)
- Antibodies, Monoclonal
(administration & dosage, metabolism, therapeutic use)
- Female
- Glycoproteins
(immunology, metabolism)
- Homeodomain Proteins
(genetics)
- Humans
- Immune Sera
(administration & dosage)
- Infusions, Intravenous
- Intestinal Mucosa
(blood supply, immunology, pathology)
- Lung
(immunology, pathology)
- Male
- Mesenteric Arteries
- Mice
- Mice, Knockout
- Receptors, Complement 3b
(deficiency, genetics, physiology)
- Receptors, Complement 3d
(deficiency, genetics, physiology)
- Reperfusion Injury
(genetics, immunology, prevention & control)
- beta 2-Glycoprotein I
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