Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice.
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.
Fleming
Sherry D
SD
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Egan
Ryan P
RP
Chai
Chunyan
C
Girardi
Guillermina
G
Holers
V Michael
VM
Salmon
Jane
J
Monestier
Marc
M
Tsokos
George C
GC
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000008:administration & dosage / Q000627:therapeutic use; D017152:Antibodies, Antiphospholipid / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries; D051379:Mice; D018345:Mice, Knockout; D017463:Receptors, Complement 3b / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D017464:Receptors, Complement 3d / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D018398:Homeodomain Proteins; D007106:Immune Sera; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D053482:beta 2-Glycoprotein I; C064658:RAG-1 protein