CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse.

CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse.
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DOI:
10.1189/jlb.0210065
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发表时间:
2010-08
影响因子:
5.5
通讯作者:
Shapiro LH
Shapiro LH
中科院分区:
医学3区
文献类型:
--
作者:
Winnicka B;O'Conor C;Schacke W;Vernier K;Grant CL;Fenteany FH;Pereira FE;Liang B;Kaur A;Zhao R;Montrose DC;Rosenberg DW;Aguila HL;Shapiro LH

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虽然骨髓标志物CD13与许多骨髓细胞功能有关,但其基因消融揭示了CD13对这些功能的名义贡献。CD13细胞表面标志物在非常早期以及分化的髓系造血细胞上的稳健和一致的表达已经促使了许多研究,这些研究试图确定CD13在髓系细胞中的作用。为了直接解决髓样CD13的功能,我们创建了CD13缺失小鼠,并在细胞测定和炎性疾病模型中评估了来自WT和CD13缺失动物的纯化的原代巨噬细胞或DC的反应,其中先前已经涉及CD13。我们发现,缺乏CD13的小鼠发育正常,造血功能正常,除了胸腺T细胞数量增加,而不是外周T细胞数量增加。此外,在体外试验中,CD13似乎在我们测试的吞噬作用、增殖和抗原呈递方面基本上是不稳定的,尽管我们观察到肌动蛋白非依赖性红细胞摄取略有下降。然而,与我们已发表的研究一致,我们表明单核细胞CD13的缺乏完全消除了抗CD13依赖性单核细胞与WT内皮细胞的粘附。四种炎性疾病模型的体内评估表明,缺乏CD13对疾病发作或进展的影响很小。CD13 WT和空巨噬细胞之间的基因表达水平的名义上的改变反对代偿机制。因此,尽管CD13在骨髓细胞上高度表达,并且是正常细胞和白血病细胞的骨髓谱系的可靠标志物,但它不是造血发育、止血或骨髓细胞功能的关键调节剂。
While the myeloid marker CD13 has been implicated in numerous myeloid cell functions, its genetic ablation reveals a nominal contribution of CD13 to these functions. The robust and consistent expression of the CD13 cell surface marker on very early as well as differentiated myeloid hematopoietic cells has prompted numerous investigations seeking to define roles for CD13 in myeloid cells. To address the function of myeloid CD13 directly, we created a CD13 null mouse and assessed the responses of purified primary macrophages or DCs from WT and CD13 null animals in cell assays and inflammatory disease models, where CD13 has been implicated previously. We find that mice lacking CD13 develop normally with normal hematopoietic profiles except for an increase in thymic but not peripheral T cell numbers. Moreover, in in vitro assays, CD13 appears to be largely dispensable for the aspects of phagocytosis, proliferation, and antigen presentation that we tested, although we observed a slight decrease in actin‐independent erythrocyte uptake. However, in agreement with our published studies, we show that lack of monocytic CD13 completely ablates anti‐CD13‐dependent monocyte adhesion to WT endothelial cells. In vivo assessment of four inflammatory disease models showed that lack of CD13 has little effect on disease onset or progression. Nominal alterations in gene expression levels between CD13 WT and null macrophages argue against compensatory mechanisms. Therefore, although CD13 is highly expressed on myeloid cells and is a reliable marker of the myeloid lineage of normal and leukemic cells, it is not a critical regulator of hematopoietic development, hemostasis, or myeloid cell function.
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