Suppression of complement activation by recombinant Crry inhibits experimental autoimmune anterior uveitis (EAAU).
Suppression of complement activation by recombinant Crry inhibits experimental autoimmune anterior uveitis (EAAU).
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DOI：
10.1016/j.molimm.2010.08.006
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发表时间：
2010-11
影响因子：
3.6
通讯作者：
Bora NS
中科院分区：
文献类型：
--
作者：
Manickam B;Jha P;Hepburn NJ;Morgan BP;Harris CL;Bora PS;Bora NS
本研究旨在探讨与大鼠IgG2a Fc部分相连的重组大鼠CRY(CRY-Ig)对实验性自身免疫性前葡萄膜炎(EAAU)的诱导和对已建立的疾病的影响。用牛黑素相关抗原(MAA)免疫Lewis大鼠，诱导EAAU。MAA致敏动物在EAAU发病前或临床发病后分别给予Crry-Ig、大鼠IgG2a(同型对照)或PBS。注射Crry-Ig可抑制EAAU的诱导，而注射IgG2a或PBS的所有动物均发展为正常的EAAU。CRRY-Ig治疗可抑制眼部补体活化和外周血中补体的功能活性。在EAAU高峰期，Crry-Ig组大鼠眼内干扰素-γ、IP-10、细胞间黏附分子-1和细胞间黏附分子-1的水平显著降低。重要的是，即使在EAAU发病后使用CRY-Ig也会导致EAAU疾病活动性和早期消退的急剧下降。总而言之，这里提出的证据表明，Crry-Ig抑制补体会导致眼睛中炎症分子-C3激活产物、MAC、细胞因子、趋化因子和黏附分子的水平降低。这些分子的下调会影响炎症细胞对眼部的渗透和募集，从而抑制EAAU。
This study was initiated to explore the effect of recombinant rat Crry linked to the Fc portion of rat IgG2a (Crry-Ig) on the induction of experimental autoimmune anterior uveitis (EAAU) and on established disease. EAAU was induced in Lewis rats by immunization with bovine melanin associated antigen (MAA). MAA sensitized animals received Crry-Ig, rat IgG2a (isotype control) or PBS separately before the onset of EAAU or after the onset of clinical disease. Administration of Crry-Ig suppressed the induction of EAAU while all animals injected with IgG2a or PBS developed the normal course of EAAU. Treatment with Crry-Ig resulted in suppression of ocular complement activation as well as the functional activity of complement in the peripheral blood. At the peak of EAAU, levels of IFN-γ, IP-10, ICAM-1 and LECAM-1 were significantly reduced within the eyes of Crry-Ig treated Lewis rats. Importantly, administration of Crry-Ig even after the onset of EAAU resulted in a sharp decline in the disease activity and early resolution of EAAU. Collectively, the evidence presented here demonstrate that inhibition of complement by Crry-Ig results in low levels of inflammatory molecules - C3 activation products, MAC, cytokines, chemokines and adhesion molecules in the eye. Down-regulation of these molecules affects the infiltration and recruitment of inflammatory cells to the eye resulting in inhibition of EAAU.
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DOI：
10.1084/jem.181.1.151
发表时间：
1995-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kim YU;Kinoshita T;Molina H;Hourcade D;Seya T;Wagner LM;Holers VM
通讯作者：
Holers VM
影响因子：
3.4
作者：
BROEKHUYSE, RM;KUHLMANN, ED;VANVUGT, AHM
通讯作者：
VANVUGT, AHM
影响因子：
4.4
作者：
Bora, Nalini S.;Kaliappan, Sankaranarayanan;Bora, Puran S.
通讯作者：
Bora, Puran S.
影响因子：
4.4
作者：
Hietala, MA;Jonsson, IM;Pekna, M
通讯作者：
Pekna, M
影响因子：
3.6
作者：
Hepburn, Natalie J.;Chamberlain-Banoub, Jayne L.;Harris, Claire L.
通讯作者：
Harris, Claire L.