| First Author | Liu YS | Year | 2019 |
| Journal | J Cell Mol Med | Volume | 23 |
| Issue | 5 | Pages | 3402-3416 |
| PubMed ID | 30869196 | Mgi Jnum | J:318644 |
| Mgi Id | MGI:6459346 | Doi | 10.1111/jcmm.14236 |
| Citation | Liu YS, et al. (2019) The pattern-recognition molecule mindin binds integrin Mac-1 to promote macrophage phagocytosis via Syk activation and NF-kappaB p65 translocation. J Cell Mol Med 23(5):3402-3416 |
| abstractText | Mindin has a broad spectrum of roles in the innate immune system, including in macrophage migration, antigen phagocytosis and cytokine production. Mindin functions as a pattern-recognition molecule for microbial pathogens. However, the underlying mechanisms of mindin-mediated phagocytosis and its exact membrane receptors are not well established. Herein, we generated mindin-deficient mice using the CRISPR-Cas9 system and show that peritoneal macrophages from mindin-deficient mice were severely defective in their ability to phagocytize E coli. Phagocytosis was enhanced when E coli or fluorescent particles were pre-incubated with mindin, indicating that mindin binds directly to bacteria or non-pathogen particles and promotes phagocytosis. We defined that (131) I-labelled mindin binds with integrin Mac-1 (CD11b/CD18), the F-spondin (FS)-fragment of mindin binds with the alphaM -I domain of Mac-1 and that mindin serves as a novel ligand of Mac-1. Blockade of the alphaM -I domain of Mac-1 using either a neutralizing antibody or si-Mac-1 efficiently blocked mindin-induced phagocytosis. Furthermore, mindin activated the Syk and MAPK signalling pathways and promoted NF-kappaB entry into the nucleus. Our data indicate that mindin binds with the integrin Mac-1 to promote macrophage phagocytosis through Syk activation and NF-kappaB p65 translocation, suggesting that the mindin/Mac-1 axis plays a critical role during innate immune responses. |
