Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q

被引:171
作者
Hart, ML
Ceonzo, KA
Shaffer, LA
Takahashi, K
Rother, RP
Reenstra, WR
Buras, JA
Stahl, GL
机构
[1] Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury,Med Sch, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Lab Dev Immunol, Boston, MA 02115 USA
[3] Alex Pharmaceut, Dept Discovery Res, Cheshire, CT 06410 USA
[4] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA
关键词
D O I
10.4049/jimmunol.174.10.6373
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Complement activation plays an important role in local and remote tissue injury associated with gastrointestinal ischemia-reperfusion (GI/R). The role of the classical and lectin complement pathways in GI/R injury was evaluated using C1q-deficient (C1q KO), MBL-A/C-deficient (MBL-null), complement factor 2- and factor B-deficient (C2/fB KO), and wild-type (WT) mice. Gastrointestinal ischemia (20 min), followed by 3-h reperfusion, induced intestinal and lung injury in C1q KO and WT mice, but not in C2/fB KO mice. Addition of human C2 to C2/fB KO mice significantly restored GI/R injury, demonstrating that GI/R injury is mediated via the lectin and/or classical pathway. Tissue C3 deposition in C1q KO and WT, but not C2/fB KO, mice after GI/R demonstrated that complement was activated in C1q KO mice. GIN significantly increased serum alanine aminotransferase, gastrointestinal barrier dysfunction, and neutrophil infiltration into the lung and gut in C1q KO and WT, but not C2/fB KO, mice. MBL-null mice displayed little gut injury after GI/R, but lung injury was present. Addition of recombinant human MBL (rhuMBL) to MBL-null mice significantly increased injury compared with MBL-null mice after GI/R and was reversed by anti-MBL mAb treatment. However, MBL-null mice were not protected from secondary lung injury after GI/R. These data demonstrate that C2 and MBL, but not C1q, are necessary for gut injury after GI/R. Lung injury in mice after GI/R is MBL and C1q independent, but C2 dependent, suggesting a potential role for ficolins in this model.
引用
收藏
页码:6373 / 6380
页数:8
相关论文
共 56 条
[41]   Role for the alternative complement pathway in ischemia/reperfusion injury [J].
Stahl, GL ;
Xu, YY ;
Hao, LM ;
Miller, M ;
Buras, JA ;
Fung, M ;
Zhao, H .
AMERICAN JOURNAL OF PATHOLOGY, 2003, 162 (02) :449-455
[42]  
Suankratay C, 1999, CLIN EXP IMMUNOL, V117, P435
[43]   The influence of intestinal ischemia and reperfusion on bidirectional intestinal barrier permeability, cellular membrane integrity, proteinase inhibitors, and cell death in rats [J].
Sun, ZW ;
Wang, XD ;
Deng, XM ;
Lasson, Å ;
Wallén, R ;
Hallberg, E ;
Andersson, R .
SHOCK, 1998, 10 (03) :203-212
[44]   A targeted disruption of the murine complement factor B gene resulting in loss of expression of three genes in close proximity, factor B, C2, and D17H6S45 [J].
Taylor, PR ;
Nash, JT ;
Theodoridis, E ;
Bygrave, AE ;
Walport, MJ ;
Botto, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (03) :1699-1704
[45]  
Tendler David A, 2003, Semin Gastrointest Dis, V14, P66
[46]   SERUM ENZYME LEVELS DURING INTESTINAL ISCHEMIA [J].
THOMPSON, JS ;
BRAGG, LE ;
WEST, WW .
ANNALS OF SURGERY, 1990, 211 (03) :369-373
[47]   Hepatic hypoperfusion after intestinal reperfusion [J].
Turnage, RH ;
Kadesky, KM ;
Myers, SI ;
Guice, KS ;
Oldham, KT .
SURGERY, 1996, 119 (02) :151-160
[48]   Bile analysis as a tool for assessing integrity of biliary epithelial cells after cold ischemia-reperfusion of rat livers [J].
Vajdová, K ;
Smreková, R ;
Kukan, M ;
Lutterová, M ;
Wsólová, L .
CRYOBIOLOGY, 2000, 41 (02) :145-152
[49]   Myocardial infarction and apoptosis after myocardial ischemia and reperfusion - Role of the terminal complement components and inhibition by anti-C5 therapy [J].
Vakeva, AP ;
Agah, A ;
Rollins, SA ;
Matis, LA ;
Li, L ;
Stahl, GL .
CIRCULATION, 1998, 97 (22) :2259-2267
[50]  
VAUGHAN WG, 1992, J PEDIATR SURG, V27, P968