| First Author | Hoshino H | Year | 2011 |
| Journal | J Histochem Cytochem | Volume | 59 |
| Issue | 6 | Pages | 572-83 |
| PubMed ID | 21430257 | Mgi Jnum | J:181015 |
| Mgi Id | MGI:5308532 | Doi | 10.1369/0022155411404416 |
| Citation | Hoshino H, et al. (2011) An integrin alpha4beta7*IgG heterodimeric chimera binds to MAdCAM-1 on high endothelial venules in gut-associated lymphoid tissue. J Histochem Cytochem 59(6):572-83 |
| abstractText | Lymphocyte homing is regulated by a multistep process mediated by sequential adhesive interactions between circulating lymphocytes and high endothelial venules (HEVs). In gut-associated lymphoid tissue (GALT), the initial interactive step, "tethering and rolling," is partly mediated by integrin alpha4beta7 expressed on GALT-homing lymphocytes and its ligand MAdCAM-1, which is exclusively expressed on HEVs in GALT. To probe functional MAdCAM-1 in tissue sections, we developed a soluble integrin alpha4beta7 heterodimeric IgG chimera by joining the extracellular region of mouse integrin alpha4 and beta7 subunits to a human IgG Fc domain. Western blot analysis revealed that co-transfection of HEK 293T cells with expression vectors encoding integrin alpha4*IgG and beta7*IgG results in the formation of alpha4beta7*IgG heterodimeric chimeras. This complex preferentially binds to CHO cells expressing MAdCAM-1 and, to a lesser extent, to cells expressing VCAM-1, but not to cells expressing ICAM-1. Moreover, alpha4beta7*IgG specifically binds to HEVs in GALT in situ in a divalent cation-dependent fashion and inhibits lymphocyte binding to HEVs in GALT. These findings indicate that alpha4beta7*IgG can be used as a probe for functional MAdCAM-1 expressed on HEVs in GALT and could potentially serve as an anti-inflammatory drug inhibiting GALT-specific lymphocyte migration. |
