Adhesion molecule-dependent mechanisms regulate the rate of macrophage clearance during the resolution of peritoneal inflammation.
Adhesion molecule-dependent mechanisms regulate the rate of macrophage clearance during the resolution of peritoneal inflammation.
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DOI：
10.1084/jem.20011794
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发表时间：
2002-12-02
期刊：
影响因子：
--
通讯作者：
Laurent GJ
中科院分区：
文献类型：
--
作者：
Bellingan GJ;Xu P;Cooksley H;Cauldwell H;Shock A;Bottoms S;Haslett C;Mutsaers SE;Laurent GJ
巨噬细胞的清除对于炎症的消退至关重要。人们对单核细胞如何进入炎症部位知之甚少，但对产生的巨噬细胞是如何清除的知之甚少。我们以前已经证明，巨噬细胞从溶解腹膜炎中清除是通过迁移到引流淋巴管而不是局部细胞凋亡来实现的。我们现在研究这一过程的机制，特别是通过评估巨噬细胞和淋巴管内细胞之间黏附相互作用的调节调节巨噬细胞清除速度的假设。我们在体内证明，巨噬细胞特异性地附着在覆盖在引流淋巴管上的间皮细胞上，其迁移率受巨噬细胞激活状态的调节。我们观察到巨噬细胞-间皮细胞黏附是精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp，RgD)敏感的，并且部分地由很晚抗原(Vla)-4和Vla-5介导，而不是α-v或β-2整合素。此外，在体内，巨噬细胞对淋巴管的清除可被RGD肽和VLA-4和VLA-5阻断，但不能被β-2阻断抗体所阻断。这是巨噬细胞从炎症部位迁移受到控制的第一个证据，并表明这是通过巨噬细胞-间皮细胞间相互作用的特异性黏附分子调节来实现的。它强调了控制细胞进入淋巴循环的黏附分子的重要性，从而为操纵炎症的消退开辟了一条新的途径。
Macrophage clearance is essential for the resolution of inflammation. Much is known about how monocytes enter the inflammatory site but little is known about how resultant macro-phages are cleared. We have previously demonstrated that macrophage clearance from resolving peritonitis occurs by emigration into draining lymphatics rather than local apoptosis. We now examine mechanisms for this process, in particular by evaluating the hypothesis that modulation of adhesion interactions between macrophages and cells lining the lymphatics regulates the rate of macrophage clearance. We demonstrate in vivo that macrophages adhere specifically to mesothelium overlying draining lymphatics and that their emigration rate is regulated by the state of macrophage activation. We observed that macrophage–mesothelial adhesion is Arg-Gly-Asp (RGD) sensitive and partially mediated by very late antigen (VLA)-4 and VLA-5 but not αv or β2 integrins. Moreover, macrophage clearance into lymphatics can be blocked in vivo by RGD peptides and VLA-4 and VLA-5 but not β2 blocking antibodies. This is the first evidence that macrophage emigration from the inflamed site is controlled and demonstrates that this is exerted through specific adhesion molecule regulation of macrophage–mesothelial interactions. It highlights the importance of adhesion molecules governing entry of cells into the lymphatic circulation, thus opening a new avenue for manipulating the resolution of inflammation.
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影响因子：
2.2
作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1164/ajrccm.162.2.9911061
发表时间：
2000-08-01
影响因子：
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作者：
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