| First Author | Liu L | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 1 | Pages | 238-47 |
| PubMed ID | 22116828 | Mgi Jnum | J:180588 |
| Mgi Id | MGI:5306680 | Doi | 10.4049/jimmunol.1102029 |
| Citation | Liu L, et al. (2012) The calcineurin B subunit (CnB) is a new ligand of integrin alphaM that mediates CnB-induced Apo2L/TRAIL expression in macrophages. J Immunol 188(1):238-47 |
| abstractText | We showed previously that the calcineurin B subunit (CnB) plays an important role in activation of peritoneal macrophage, but the underlying mechanism remained unknown. To examine whether there is a CnB receptor on peritoneal macrophages, we performed the radioligand binding assay of receptors. The receptor saturation binding curve demonstrated high-affinity and specific binding; the maximum binding was 1090 fmol/10(5) cells, and the K(d) was 70.59 pM. Then, we used a CnB affinity resin to trap potential receptors from highly purified peritoneal macrophage membranes. Mass spectrometry analysis showed that the binding protein was mouse integrin alphaM. We next performed a competition binding experiment to confirm the binding of CnB to integrin alphaM. This showed that FITC-CnB bound specifically to peritoneal macrophages and that binding was blocked by the addition of integrin alphaM Ab. We observed that CnB could induce TRAIL gene expression in peritoneal macrophages in vitro and in vivo. Integrin alphaM Ab blocking, RNA interference, and ligand competition experiments demonstrated that CnB-induced TRAIL expression is dependent on integrin alphaM. Furthermore, the tumoricidal activity of CnB-activated peritoneal macrophages is partially dependent on TRAIL. In addition, CnB treatment significantly prolongs the survival of mice bearing H22 ascites tumors, which has a positive correlation with the induction level of TRAIL. These results reveal a novel function of the CnB in innate immunity and cancer surveillance. They also point to a new signaling pathway leading to induction of TRAIL and suggest a possible application of CnB in cancer therapy. |
