Natural immunoglobulin M initiates an inflammatory response important for both hepatic ischemia reperfusion injury and regeneration in mice.
Natural immunoglobulin M initiates an inflammatory response important for both hepatic ischemia reperfusion injury and regeneration in mice.
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DOI：
10.1002/hep.29512
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Tomlinson S
中科院分区：
文献类型：
--
作者：
Marshall K;Jin J;Atkinson C;Alawieh A;Qiao F;Lei B;Chavin KD;He S;Tomlinson S
Complement plays a role in both hepatic ischemia reperfusion (IR) injury (IRI) and liver regeneration, but it is not clear how complement is activated in either process. We investigated the role of self-reactive IgM antibodies in activating complement after hepatic IR and liver resection. Natural IgM antibodies that recognize danger associated molecular patterns (neoepitopes) activate complement following both hepatic IR and liver resection. Antibody-deficient Rag1−/− mice were protected from hepatic IRI, but had increased hepatic injury and an impaired regenerative response after 70% partial hepatectomy (PHx). We identified two IgM mAbs that specifically reversed the effect of Rag1 deficiency in both models; B4 (recognizes annexin IV) and C2 (recognizes subset of phospholipids). Focusing on the B4-specific response, we demonstrated sinusoidal colocalization of IgM and C3d in Rag1−/− mice that were reconstituted with B4 mAb, and further that the annexin IV neoepitope is specifically and similarly expressed after both hepatic IR and PHx in wild-type mice. A single-chain Ab construct (scFv) derived from B4 mAb blocked IgM binding and reduced injury after IR in wild-type mice, although interestingly B4scFv did not alter regeneration following PHx, indicating that anti-annexin IV antibodies are sufficient, but not necessary for the regenerative response in the context of an entire natural antibody repertoire. We also demonstrated expression of the B4 neoepitope in post-ischemic human liver samples obtained after transplantation, and a corollary depletion in IgM recognizing the B4 and C2 neoepitopes in patient sera following liver transplantation. These data indicate an important role for IgM in hepatic IRI and regeneration, with a similar cross-species injury-specific recognition system that has implications for the design of neoepitope targeted therapeutics.
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DOI：
10.4049/jimmunol.1102132
发表时间：
2012-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Elvington A;Atkinson C;Kulik L;Zhu H;Yu J;Kindy MS;Holers VM;Tomlinson S
通讯作者：
Tomlinson S
DOI：
10.4049/jimmunol.0803980
发表时间：
2009-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kulik L;Fleming SD;Moratz C;Reuter JW;Novikov A;Chen K;Andrews KA;Markaryan A;Quigg RJ;Silverman GJ;Tsokos GC;Holers VM
通讯作者：
Holers VM
影响因子：
29.4
作者：
Tumanov AV;Koroleva EP;Christiansen PA;Khan MA;Ruddy MJ;Burnette B;Papa S;Franzoso G;Nedospasov SA;Fu YX;Anders RA
通讯作者：
Anders RA
DOI：
10.1084/jem.183.5.2343
发表时间：
1996-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Weiser MR;Williams JP;Moore FD Jr;Kobzik L;Ma M;Hechtman HB;Carroll MC
通讯作者：
Carroll MC
影响因子：
15.9
作者：
He, Songqing;Atkinson, Carl;Tomlinson, Stephen
通讯作者：
Tomlinson, Stephen