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首页> 外文期刊>Comparative Medicine >Leukotoxin Kills Rodent WBC by Targeting Leukocyte Function Associated Antigen 1
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Leukotoxin Kills Rodent WBC by Targeting Leukocyte Function Associated Antigen 1

机译：白细胞毒素通过靶向白细胞功能相关抗原1杀死啮齿类动物白细胞。

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摘要

Leukotoxin is a protein that is secreted by Aggregatibacter actinomycetemcomitans and that primarily targets the active form of leukocyte function associated antigen 1 (LFA1) on WBC. Because of its specificity for WBC, leukotoxin is being developed asa novel biologic treatment for hematologic malignancies and autoimmune-inflammatory diseases. Early studies indicated that leukotoxin is specific for WBC from humans and Old World primates. In the current study, we used in vivo and in vitro assays to show that leukotoxin has a wider host range than previously believed and can kill rodent WBC. Administration of leukotoxin to rats and mice resulted in a rapid drop in WBC number but had no effect on RBC or platelet counts. Using LFAl-knockout mice, we showed that leukotoxin-mediated depletion of WBC is dependent on LFA1. In addition, similar to its effect on human monocytes, leukotoxin kills murine myeloid leukemia via a lysosome-mediated pathway that is dependent on cathepsin D. This newly described broader host range of leukotoxin enables the biology of the protein to be studied in rodent species and offers the possibility of using rodent models for evaluating the therapeutic efficacy of leukotoxin in various diseases.
机译：白细胞毒素是由放线杆菌聚集的分泌蛋白，主要靶向白细胞功能相关抗原1（LFA1）的活性形式。由于其对白细胞的特异性，白细胞毒素正在被开发为一种针对血液系统恶性肿瘤和自身免疫性炎症疾病的新型生物疗法。早期研究表明，白细胞毒素对人类和旧世界灵长类动物的白细胞具有特异性。在当前的研究中，我们使用了体内和体外试验来证明白细胞毒素的宿主范围比以前认为的要广，并且可以杀死啮齿类动物白细胞。向大鼠和小鼠施用白细胞毒素导致WBC数量快速下降，但对RBC或血小板计数没有影响。使用LFAl基因敲除小鼠，我们表明白细胞毒素介导的WBC耗竭取决于LFA1。此外，类似于其对人类单核细胞的作用，白细胞毒素通过依赖组织蛋白酶D的溶酶体介导的途径杀死鼠骨髓性白血病。这种新近描述的更广泛的白细胞毒素宿主范围使该蛋白质的生物学特性得以在啮​​齿动物中研究。提供了使用啮齿动物模型评估白细胞毒素在各种疾病中的治疗效果的可能性。

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