Anti-ribonucleoprotein antibodies mediate enhanced lung injury following mesenteric ischemia/reperfusion in Rag-1-l- mice

Michael P. Keith, Chantal Moratz, Ryan Egan, Athina Zacharia, Eric L. Greidinger, Robert W. Hoffman, George C. Tsokos

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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-l- animals. Rag1-l- 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.

Original languageEnglish (US)
Pages (from-to)208-216
Number of pages9
JournalAutoimmunity
Volume40
Issue number3
DOIs
StatePublished - May 1 2007

Keywords

  • Complement
  • Inflammation
  • Ischemia/reperfusion
  • Ribonucleoprotein (RNP) antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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