Localization of marginal zone macrophages is regulated by C-C chemokine ligands 21/19
Localization of marginal zone macrophages is regulated by C-C chemokine ligands 21/19
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DOI：
10.4049/jimmunol.173.8.4815
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发表时间：
2004-10-15
影响因子：
4.4
通讯作者：
Kaye, PM
中科院分区：
文献类型：
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作者：
Ato, M;Nakano, H;Kaye, PM
脾脏边缘区是捕获血源性病原体的重要部位，也是淋巴细胞进入白色髓的通道。我们最近报道了杜氏利什曼原虫感染导致MZ巨噬细胞（MZM）从MZ的显着选择性损失。为了理解这一观察结果的基础，我们研究了MZM如何在未感染小鼠中维持其稳态解剖分布。我们现在报告plt/plt小鼠，缺乏功能性CCL 19和CCL 21，与正常C57 BL/6（B6）小鼠相比，MZM的数量显著减少。类似地，在B6.CD45.1-->plt/plt嵌合体中，与在相反的plt/plt-->B6.CD45.1嵌合体中观察到的数量相比，供体来源的MZM是罕见的。此外，我们发现，百日咳毒素，一种趋化因子受体信号传导的抑制剂，给B6小鼠的结果退出MZ的MZM，MZM可以迁移响应CCL 19和CCL 21在体外，MZM与CD 31（+）CCL 21（+）内皮细胞共定位。总的来说，这些数据表明，CCL 21，并在较小程度上，CCL 19发挥显着的作用，在独特的定位MZM脾MZ。CCL 19和CCL 21的缺乏，如先前在感染L. donovani，因此可以解释在这种感染期间观察到的MZM的选择性损失。
The marginal zone (MZ) of the spleen is an important site for the capture of blood-borne pathogens and a gateway for lymphocytes entering the white pulp. We have recently reported that Leishmania donovani infection results in a remarkably selective loss of MZ macrophages (MZM) from the MZ. To understand the basis of this observation, we have investigated how MZM maintain their anatomical distribution in the steady state in uninfected mice. We now report that plt/plt mice, which lack functional CCL19 and CCL21, have significantly reduced numbers of MZM compared with normal C57BL/6 (B6) mice. Similarly, in B6.CD45.1-->plt/plt chimeras, donor-derived MZM were rare compared with the number observed in reciprocal plt/plt-->B6.CD45.1 chimeras. Moreover, we show that administration of pertussis toxin, an inhibitor of chemokine receptor signaling, to B6 mice results in exit of MZM from the MZ, that MZM can migrate in response to CCL19 and CCL21 in vitro, and that MZM colocalize with CD31(+)CCL21(+) endothelial cells. Collectively, these data indicate that CCL21 and, to a lesser extent, CCL19 play significant roles in the distinctive localization of MZM within the splenic MZ. Deficiency of CCL19 and CCL21, as also previously observed in mice infected with L. donovani, may thus account for the selective loss of MZM seen during this infection.