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骆驼体内产生的抗体可阻断人嗜碱性粒细胞中组胺的释放和 IgE 与 FcεRI 的结合。

Blocking of Histamine Release and IgE Binding to FcεRI on Human Basophils by Antibodies Produced in Camels.

机构信息

Department of Biological Sciences-Yarmouk University, Irbid, Jordan.

Jordan Company for Antibody Production (MONOJO), Amman, Jordan.

出版信息

Allergy Asthma Immunol Res. 2015 Nov;7(6):583-9. doi: 10.4168/aair.2015.7.6.583. Epub 2015 Jun 25.

Abstract

PURPOSE

The production of camel heavy-chain antihuman IgE (huIgE) that has the potential to block IgE-FcεRI interaction and histamine release by basophils.

METHODS

Camels were immunized with a synthetic loop peptide (SLP) designed in a multiple antigen peptide system (MAPS) forming SLP-MAPS immunogen. Camel polyclonal antibodies (PCAs) were produced, purified, characterized using Protein A & G, ELISA, and SDS-PAGE, and tested for their potency to block passive sensitization and histamine release of human basophils using flow cytometry (FCM) and ELISA, respectively.

RESULTS

FCM data indicated that camel conventional (IgG1) and heavy chain antibodies (HCAbs; IgG2, and IgG3) had blocking activities of 43.9%, 72%, and 96.6%, respectively. Moreover, both IgG2 and IgG3 achieved remarkable inhibition rates of 93.98% and 97.05% in histamine release, respectively, whereas the IgG1inhibiting activity was 60.05%.

CONCLUSIONS

Camel PCAs produced against SLP-MAPS were capable of blocking the IgE-receptor interaction and the release of histamine by basophils with superiority to HCAbs. These findings may pave the way toward the possible use of camel anti-huIgE HCAbs as blocking antibodies in the treatment of IgE-mediated allergy and asthma.

摘要

目的

产生骆驼重链抗人 IgE(huIgE),该抗体具有阻断 IgE-FcεRI 相互作用和嗜碱性粒细胞释放组胺的潜力。

方法

骆驼通过设计在多抗原肽系统 (MAPS) 中的合成环肽 (SLP) 进行免疫,形成 SLP-MAPS 免疫原。制备、纯化骆驼多克隆抗体 (PCAs),并使用蛋白 A 和 G、ELISA 和 SDS-PAGE 进行表征,分别使用流式细胞术 (FCM) 和 ELISA 测试其阻断人嗜碱性粒细胞被动致敏和组胺释放的效力。

结果

FCM 数据表明,骆驼常规(IgG1)和重链抗体(HCAbs;IgG2 和 IgG3)的阻断活性分别为 43.9%、72%和 96.6%。此外,IgG2 和 IgG3 分别实现了组胺释放的 93.98%和 97.05%的显著抑制率,而 IgG1 的抑制活性为 60.05%。

结论

针对 SLP-MAPS 产生的骆驼 PCAs 能够阻断 IgE 受体相互作用和嗜碱性粒细胞释放组胺,其作用优于 HCAbs。这些发现可能为骆驼抗 huIgE HCAbs 作为 IgE 介导的过敏和哮喘治疗中的阻断抗体的可能用途铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/680a/4605931/3dbd821379f7/aair-7-583-g001.jpg

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