The Upregulation of Integrin α(D)β(2) (CD11d/CD18) on Inflammatory Macrophages Promotes Macrophage Retention in Vascular Lesions and Development of Atherosclerosis.
The Upregulation of Integrin α(D)β(2) (CD11d/CD18) on Inflammatory Macrophages Promotes Macrophage Retention in Vascular Lesions and Development of Atherosclerosis.
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DOI：
10.4049/jimmunol.1602175
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发表时间：
2017-06-15
期刊：
影响因子：
--
通讯作者：
Yakubenko VP
中科院分区：
文献类型：
--
作者：
Aziz MH;Cui K;Das M;Brown KE;Ardell CL;Febbraio M;Pluskota E;Han J;Wu H;Ballantyne CM;Smith JD;Cathcart MK;Yakubenko VP
巨噬细胞聚集是慢性炎症发展过程中的关键步骤，启动了许多破坏性疾病的进展。白细胞特异性整合素αDβ2(CD11d/CD18)在炎症部位的巨噬细胞上显著上调。先前我们发现CD11d在细胞表面的过度表达由于过度黏附而抑制了细胞的体外迁移。在这里，我们研究了炎症介导的CD11d上调如何在动脉粥样硬化形成过程中促进巨噬细胞滞留在炎症部位。CD11d−/−/ApoE−/−小鼠在16周后接受西方饮食，以评估动脉粥样硬化。CD11d缺乏导致主动脉和分离的巨噬细胞中脂质沉积显著减少。CD11d−/−小鼠主动脉窦巨噬细胞数量减少，但不影响其细胞的凋亡和增殖。将荧光标记的野生型和CD11d−/−单核细胞过继转移到载脂蛋白E−/−小鼠体内，显示出类似的循环募集，但减少了CD11d−/−巨噬细胞在主动脉内的聚集。此外，CD11d在动脉粥样硬化病变的巨噬细胞和体外培养的M1巨噬细胞上的表达显著上调。有趣的是，相关的配体共享整合素CD11b的表达没有改变。这种差异决定了它们在巨噬细胞迁移调节中的不同作用。CD11d缺乏的M1巨噬细胞在三维纤维蛋白基质和腹膜炎症消退过程中表现出更好的迁移能力，而CD11b−/−M1巨噬细胞的迁移没有受到影响。这些结果证实了高密度CD11d在动脉粥样硬化形成过程中对巨噬细胞停滞的作用。由于CD11d在多种炎症依赖性疾病中均有高表达，我们认为促炎症巨噬细胞上CD11d/CD18的上调可能是巨噬细胞滞留在炎症部位的共同机制，从而促进慢性炎症和疾病的发展。
Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin αDβ2 (CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration due to excessive adhesion. Here we have investigated how inflammation-mediated CD11d upregulation contributes to macrophage retention at inflammatory sites during atherogenesis. Atherosclerosis was evaluated in CD11d−/−/ApoE−/− mice after 16 weeks on a Western diet. CD11d deficiency led to a marked reduction in lipid deposition in aortas and isolated macrophages. Macrophage numbers in aortic sinuses of CD11d−/− mice were reduced without affecting their apoptosis and proliferation. Adoptive transfer of fluorescently-labeled wild-type and CD11d−/− monocytes into ApoE−/− mice demonstrated similar recruitment from circulation, but reduced accumulation of CD11d−/− macrophages within the aortas. Furthermore, CD11d expression was significantly upregulated on macrophages in atherosclerotic lesions and M1 macrophages in vitro. Interestingly, expression of the related ligand-sharing integrin CD11b was not altered. This difference defines their distinct roles in the regulation of macrophage migration. CD11d-deficient M1 macrophages demonstrated improved migration in a three-dimensional fibrin matrix and during resolution of peritoneal inflammation, while migration of CD11b−/− M1 macrophages was not affected. These results prove the contribution of high densities of CD11d to macrophage arrest during atherogenesis. Since high expression of CD11d was detected in several inflammation-dependent diseases, we suggest that CD11d/CD18 upregulation on pro-inflammatory macrophages may represent a common mechanism for macrophage retention at inflammatory sites, thereby promoting chronic inflammation and disease development.
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影响因子：
3
作者：
de Azevedo-Quintanilha IG;Vieira-de-Abreu A;Ferreira AC;Nascimento DO;Siqueira AM;Campbell RA;Teixeira Ferreira TP;Gutierrez TM;Ribeiro GM;E Silva PM;Carvalho AR;Bozza PT;Zimmerman GA;Castro-Faria-Neto HC
通讯作者：
Castro-Faria-Neto HC
影响因子：
6
作者：
Antonov, AS;Kolodgie, FD;Gerrity, RG
通讯作者：
Gerrity, RG
影响因子：
10.8
作者：
Merched, Aksam;Tollefson, Katherine;Chan, Lawrence
通讯作者：
Chan, Lawrence
在动脉粥样硬化之前和开发过程中淋巴细胞募集到主动脉壁是部分依赖性L-选择蛋白。
DOI：
10.1084/jem.20052205
发表时间：
2006-05-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1084/jem.20011794
发表时间：
2002-12-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bellingan GJ;Xu P;Cooksley H;Cauldwell H;Shock A;Bottoms S;Haslett C;Mutsaers SE;Laurent GJ
通讯作者：
Laurent GJ