Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes
Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes
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DOI：
10.1136/ard.2006.064626
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发表时间：
2007-12-01
影响因子：
27.4
通讯作者：
Kallenberg, Cees G. M.
中科院分区：
文献类型：
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作者：
van der Geld, Ymke M.;Hellmark, Thomas;Kallenberg, Cees G. M.
目的：方法：用重组人PR 3（HPR 3）、重组鼠PR 3（mPR 3）、单个嵌合人/鼠PR 3（HHm、HmH、mHH、mmH、mHm、Hmm）或嵌合蛋白池免疫大鼠和小鼠，并观察其对PR 3自身抗体的诱导作用。通过ELISA测量针对mPR 3和HPR 3的抗体。通过大鼠白色血细胞的间接免疫荧光（IIF）测定大鼠PR 3抗体。通过试纸分析进行尿分析。结果：在小鼠中，用嵌合的人/小鼠PR 3 Hmm免疫导致对mPR 3的自身抗体应答。用嵌合的人/小鼠PR 3 Hmm、HmH和mmH或嵌合的人/小鼠PR 3蛋白的库免疫的大鼠产生选择性结合大鼠粒细胞的抗体，如通过IIF检测的。结论：人/鼠嵌合蛋白免疫小鼠可诱导产生抗PR 3自身抗体。嵌合蛋白可以在开发自身免疫性疾病的实验模型中发挥作用。
Aim: In this study, we employed chimeric human/ mouse Proteinase 3 ( PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice.Method: Rats and mice were immunised with recombinant human PR3 ( HPR3), recombinant murine PR3 ( mPR3), single chimeric human/ mouse PR3 ( HHm, HmH, mHH, mmH, mHm, Hmm) or pools of chimeric proteins. Antibodies to mPR3 and HPR3 were measured by ELISA. Antibodies to rat PR3 were determined by indirect immunofluorescence ( IIF) on rat white blood cells. Urinalysis was performed by dipstick analysis. Kidney and lung tissue was obtained for pathological examination.Results: In mice, immunisation with the chimeric human/ mouse PR3 Hmm led to an autoantibody response to mPR3. Rats immunised with the chimeric human/ mouse PR3 Hmm, HmH and mmH, or a pool of the chimeric human/ mouse PR3 proteins, produced antibodies selectively binding to rat granulocytes as detected by IIF. No gross pathological abnormalities could be detected in kidney or lungs of mice or rats immunised with chimeric human/ mouse PR3.Conclusion: Immunisation with chimeric human/ mouse proteins induces autoantibodies to PR3 in rats and mice. Chimeric proteins can be instrumental in developing experimental models for autoimmune diseases.