Anti-ribonucleoprotein antibodies mediate enhanced lung injury following mesenteric ischemia/reperfusion in Rag-1(-/-) mice.
Natural Abs and autoantibodies bind antigens displayed by ischemia-conditioned tissues, followed by complement activation and enhanced tissue injury during reperfusion. Anti-ribonucleoprotein (RNP) Ab is associated with lung disease in patients with autoimmune disease but it is not known whether these abs contribute to lung injury. Mesenteric I/R in mice leads to local and remote lung injury. Accordingly, we used this model to investigate whether anti-RNP Abs would reconstitute I/R damage with prominent lung damage in injury-resistant Rag1(-/-) animals. Rag1(-/-) mice injected with anti-RNP Ab containing serum and subjected to mesenteric I/R suffered greater intestinal injury than control-treated and sham-operated animals. The magnitude of the reconstituted damage was anti-RNP Ab titer-dependent. Anti-RNP Ab-treated animals demonstrated a dose-dependent increase in lung histologic injury scores compared to control and sham animals. Anti-RNP mediated injury was shown to be complement dependent. These experiments reveal a novel mechanism whereby anti-RNP Abs contributes to the development of pulmonary pathology in patients with autoimmune diseases following exposure of remote organs to I/R injury.
Keith
Michael P
MP
Department of Rheumatology, National Naval Medical Center, Bethesda, MD, USA.
Moratz
Chantal
C
Egan
Ryan
R
Zacharia
Athina
A
Greidinger
Eric L
EL
Hoffman
Robert W
RW
Tsokos
George C
GC
D000818:Animals; D000974:Antibodies, Antinuclear / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012261:Ribonucleoproteins / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D000974:Antibodies, Antinuclear; D018398:Homeodomain Proteins; D012261:Ribonucleoproteins; C064658:RAG-1 protein