A Notch Ligand, Delta-Like 1 Functions As an Adhesion Molecule for Mast Cells
A Notch Ligand, Delta-Like 1 Functions As an Adhesion Molecule for Mast Cells
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DOI：
10.4049/jimmunol.1000195
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发表时间：
2010-10-01
影响因子：
4.4
通讯作者：
Hayashi, Shin-Ichi
中科院分区：
文献类型：
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作者：
Murata, Akihiko;Okuyama, Kazuki;Hayashi, Shin-Ichi
肥大细胞(MC)聚集在慢性炎症部位；然而，目前还不清楚哪些黏附分子参与了这一过程。最近，有报道称Notch配体在炎症部位表达上调。虽然Notch受体是已知的可以激活整合素的信号分子，但它们对MCs黏附的作用尚未被研究。在这项研究中，我们证明了小鼠MC有效地黏附于被迫表达Notch配体Delta-like 1(DLL1)的基质细胞。令人惊讶的是，这种粘连是MC和表达DLL1的基质细胞之间直接细胞间相互作用的结果，而不是激活Notch受体(S)-DLL1下游效应器的结果。即使细胞代谢受阻，巨噬细胞对表达Dll1的基质细胞的黏附仍然存在。这种识别只能通过加入可溶性DLL1或抗DLL1或Notch2的单抗来抑制Notch受体(S)与DLL1的相互作用而被阻断。综上所述，这些结果表明，Notch受体(S)和DLL1作为黏附分子直接促进MCs与基质细胞的黏附。对Notch受体-配体相互作用具有黏附功能的认识将为MC聚集到炎症部位的分子基础提供重要线索。《免疫学杂志》，2010,185：3905-3912。
Mast cells (MCs) accumulate in chronic inflammatory sites; however, it is not clear which adhesion molecules are involved in this process. Recently, the expression of Notch ligands was reported to be upregulated in inflammatory sites. Although Notch receptors are known as signaling molecules that can activate integrins, their contributions to the adhesion of MCs have not been studied. In this study, we demonstrated that mouse MCs efficiently adhered to stromal cells forced to express a Notch ligand, Delta-like 1 (Dll1). Surprisingly, the adhesion was a consequence of direct cell-cell interaction between MCs and Dll1-expressing stromal cells rather than activation of downstream effectors of Notch receptor(s)-Dll1. The adhesion of MCs to Dll1-expressing stromal cells remained even when the cell metabolism was arrested. The recognition was blocked only by inhibition of Notch receptor(s)-Dll1 interaction by addition of soluble DLL1, or mAbs against Dll1 or Notch2. Taken together, these results indicate that Notch receptor(s) and Dll1 directly promote the adhesion of MCs to stromal cells by acting as adhesion molecules. This appreciation that Notch receptor-ligand interactions have an adhesion function will provide an important clue to molecular basis of accumulation of MCs to inflammatory sites. The Journal of Immunology, 2010, 185: 3905-3912.