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

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(-/-) 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.

journal_name

Autoimmunity

journal_title

Autoimmunity

authors

Keith MP,Moratz C,Egan R,Zacharia A,Greidinger EL,Hoffman RW,Tsokos GC

doi

10.1080/08916930701262986

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

208-16

issue

3

eissn

0891-6934

issn

1607-842X

pii

777457874

journal_volume

40

pub_type

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