ARE MURINE MARGINAL-ZONE MACROPHAGES THE SPLENIC WHITE PULP ANALOG OF HIGH ENDOTHELIAL VENULES
ARE MURINE MARGINAL-ZONE MACROPHAGES THE SPLENIC WHITE PULP ANALOG OF HIGH ENDOTHELIAL VENULES
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DOI：
10.1002/eji.1830251127
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发表时间：
1995-11-01
影响因子：
5.4
通讯作者：
PARISH, CR
中科院分区：
文献类型：
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作者：
LYONS, AB;PARISH, CR
与淋巴结相比，淋巴细胞进入脾脏不涉及高内皮微静脉 (HEV) 相互作用。淋巴细胞进入脾脏淋巴区域的精确进入点以及机制仍然存在争议。我们详细研究了两种药物——百日咳毒素（PT）和硫酸化多糖岩藻依聚糖对脾淋巴细胞进入和定位的影响。这些先前已被证明可以干扰 HEV 中的淋巴细胞外渗。 PT 可防止淋巴细胞外渗，但不会与 HEV 结合，而岩藻依聚糖可防止结合，从而防止随后的外渗。本文介绍的研究表明，用 PT 对小鼠淋巴细胞进行预处理不会在数值上影响进入脾脏的数量，但会深刻改变淋巴细胞在脾脏内的定位。当荧光标记、PT 处理的淋巴细胞被静脉注射时，它们最初聚集在边缘区，与边缘区巨噬细胞层 (MZM phi) 明显相关，后者在白牙髓周围形成外壳。它们无法穿过该层进入白髓，随后定位在红髓中。相反，未经处理的细胞最初出现在边缘区，然后在穿过 MZM phi, 层后继续迁移到白髓中。静脉内给予岩藻依聚糖会破坏邻近 MZM phi 层的 PT 预处理淋巴细胞的定位。使用流式细胞术检测 MZM phi 和淋巴细胞之间的聚集，我们证实岩藻依聚糖也能够在体外抑制这种关联，而 PT 对这种相互作用没有影响。我们认为小鼠中的 MZM phi 是 HEV 的脾脏类似物，形成淋巴细胞进入脾白髓的端口。
The entry of lymphocytes into the spleen, in contrast to lymph nodes, does not involve high endothelial venule (HEV) interaction. The precise point of entry, as well as the mechanism by which lymphocytes enter the lymphoid areas of the spleen, remains controversial. We examined in detail the effect of two agents, pertussis toxin (PT) and the sulfated polysaccharide fucoidan, on splenic lymphocyte entry and positioning. These have previously been shown to interfere with lymphocyte extravasation across HEV. PT prevents lymphocyte extravasation, but not binding, to HEV, whereas fucoidan prevents binding and thus subsequent extravasation. Studies presented here show that pretreatment of murine lymphocytes with PT does not numerically affect entry into spleen, but profoundly alters lymphocyte positioning within the spleen. When fluorescently labeled, PT-treated lymphocytes are injected intravenously, they initially accumulate in the marginal zone, in apparent association with the layer of marginal zone macrophages (MZM phi) which form a shell around the white pulp. They fail to traverse this layer into the white pulp, and subsequently localize in the red pulp. In contrast, untreated cells initially appear in the marginal zone, then continue to migrate into the white pulp after traversing the MZM phi, layer. The localization of PT-pretreated lymphocytes adjacent to the MZM phi layer is disrupted by intravenous administration of fucoidan. Using a flow cytometric assay of aggregation between MZM phi and lymphocytes, we confirmed that fucoidan is also able to inhibit this association in vitro, whereas PT has no effect on this interaction. We propose that MZM phi in the mouse are the splenic analog of HEV, forming the port of entry of lymphocytes into the white pulp of the spleen.