Institute for Molecular and Clinical Immunology, Otto von Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Cell Commun Signal. 2012 Jun 6;10(1):14. doi: 10.1186/1478-811X-10-14.
The cytosolic adaptor protein ADAP (adhesion and degranulation promoting adapter protein) is expressed by T cells, natural killer cells, myeloid cells and platelets. ADAP is involved in T-cell-receptor-mediated inside-out signaling, which leads to integrin activation, adhesion and reorganization of the actin cytoskeleton. However, little is known about the role of ADAP in myeloid cells. In the present study, we analyzed the function of ADAP in bone-marrow-derived dendritic cells (BMDCs) from ADAP-deficient mice.
ADAP-deficient BMDCs showed almost normal levels of antigen uptake, adhesion, maturation, migration from the periphery to the draining lymph nodes, antigen-specific T-cell activation, and production of the proinflammatory cytokines IL-6 and TNF-∝. Furthermore, we provide evidence that the activation of signaling pathways after lipopolysaccharide (LPS) stimulation are not affected by the loss of ADAP. In contrast, ADAP-deficient BMDCs showed defects in CD11c-mediated cellular responses, with significantly diminished production of IL-6, TNF-∝ and IL-10. Actin polymerization was enhanced after CD11c integrin stimulation.
In summary, we propose that the adapter molecule ADAP is critical for selected CD11c integrin-mediated functions of dendritic cells.
细胞质衔接蛋白 ADAP（黏附与脱粒促进衔接蛋白）由 T 细胞、自然杀伤细胞、髓样细胞和血小板表达。ADAP 参与 T 细胞受体介导的外向信号转导，导致整合素激活、黏附和肌动蛋白细胞骨架的重排。然而，ADAP 在髓样细胞中的作用知之甚少。在本研究中，我们分析了 ADAP 缺陷型骨髓来源树突状细胞（BMDCs）中的 ADAP 功能。
ADAP 缺陷型 BMDCs 的抗原摄取、黏附、成熟、从外周向引流淋巴结的迁移、抗原特异性 T 细胞激活以及促炎细胞因子 IL-6 和 TNF-∝的产生几乎处于正常水平。此外，我们提供的证据表明，脂多糖（LPS）刺激后信号通路的激活不受 ADAP 缺失的影响。相反，ADAP 缺陷型 BMDCs 在 CD11c 介导的细胞反应中存在缺陷，IL-6、TNF-∝和 IL-10 的产生明显减少。CD11c 整合素刺激后肌动蛋白聚合增强。
综上所述，我们提出衔接分子 ADAP 对树突状细胞的某些 CD11c 整合素介导的功能至关重要。
Zotero 插件
