A Notch ligand, Delta-like 1 functions as an adhesion molecule for mast cells.
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.
Murata
Akihiko
A
Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Japan. muratako@med.tottori-u.ac.jp
Okuyama
Kazuki
K
Sakano
Seiji
S
Kajiki
Masahiro
M
Hirata
Tomohisa
T
Yagita
Hideo
H
Zúñiga-Pflücker
Juan Carlos
JC
Miyake
Kensuke
K
Akashi-Takamura
Sachiko
S
Moriwaki
Sawako
S
Niida
Shumpei
S
Yoshino
Miya
M
Hayashi
Shin-ichi
S
D000818:Animals; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051880:Receptors, Notch / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch