Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice.

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.

• 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.)

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

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