Anti-Phospholipid Antibodies Restore Mesenteric Ischemia/Reperfusion-Induced Injury in Complement Receptor 2/Complement Receptor 1-Deficient Mice

• Published in: The Journal of immunology (1950) Vol. 173; no. 11; pp. 7055 - 7061
• Main Authors: Fleming, Sherry D, Egan, Ryan P, Chai, Chunyan, Girardi, Guillermina, Holers, V. Michael, Salmon, Jane, Monestier, Marc, Tsokos, George C
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.12.2004
• Subjects: Animals; Antibodies, Anticardiolipin - administration & dosage; Antibodies, Anticardiolipin - therapeutic use; Antibodies, Antiphospholipid - administration & dosage; Antibodies, Antiphospholipid - metabolism; Antibodies, Antiphospholipid - therapeutic use; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal - therapeutic use; beta 2-Glycoprotein I; Female; Glycoproteins - immunology; Glycoproteins - metabolism; Homeodomain Proteins - genetics; Humans; Immune Sera - administration & dosage; Infusions, Intravenous; Intestinal Mucosa - blood supply; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; Lung - immunology; Lung - pathology; Male; Mesenteric Arteries; Mice; Mice, Knockout; Receptors, Complement 3b - deficiency; Receptors, Complement 3b - genetics; Receptors, Complement 3b - physiology; Receptors, Complement 3d - deficiency; Receptors, Complement 3d - genetics; Receptors, Complement 3d - physiology; Reperfusion Injury - genetics; Reperfusion Injury - immunology; Reperfusion Injury - prevention & control
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.11.7055

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.