Resolution of cutaneous inflammation after local elimination of macrophages

Resolution of cutaneous inflammation after local elimination of macrophages
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DOI:
10.1038/71908
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发表时间:
2000-01-01
影响因子:
46.9
通讯作者:
van de Winkel, JGJ
van de Winkel, JGJ
中科院分区:
工程技术1区
文献类型:
--
作者:
Thepen, T;van Vuuren, AJH;van de Winkel, JGJ

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我们构建了一种免疫毒素,由针对高亲和力IgG受体CD64和蓖麻毒素A的抗体组成,目的是通过消除活化的巨噬细胞来解决慢性炎症。在体外,这种免疫毒素被证明在诱导活化的巨噬细胞凋亡方面非常有效,使静息和低CD64表达的巨噬细胞不受影响。我们使用表达人CD64的转基因小鼠,在十二烷基硫酸钠(SLS)诱导的皮肤炎症模型中检测了我们的免疫毒素的活性。皮内注射免疫毒素(IT)后,皮肤炎症在24小时内消退。这在组织学上通过清除所有表达CD64的巨噬细胞,然后清除其他炎性细胞来证明。与炎症相关的临床参数,如局部皮肤温度和血管舒张,也有所下降。
We constructed an immunotoxin, composed of an antibody directed against the high-affinity IgG receptor CD64 and Ricin-A, with the aim of resolving chronic inflammation through elimination of activated macrophages, In vitro, this immunotoxin proved very efficient in inducing apoptosis in activated macrophages, leaving resting and low CD64-expressing macrophages unaffected. We examined the activity of our immunotoxin in a sodium lauryl sulfate (SLS)-induced cutaneous inflammation model, using transgenic mice expressing human CD64. Upon intradermal injection of the immunotoxin (IT), cutaneous inflammation resolved in 24 h. This was demonstrated histologically by clearance of all CD64-expressing macrophages, followed by clearance of other inflammatory cells. Clinical parameters associated with inflammation, such as local skin temperature and vasodilation, also decreased.