| First Author | Podolnikova NP | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 8 | Pages | 2105-2116 |
| PubMed ID | 27315778 | Mgi Jnum | J:234281 |
| Mgi Id | MGI:5789671 | Doi | 10.1016/j.ajpath.2016.04.001 |
| Citation | Podolnikova NP, et al. (2016) The Role of Integrins alphaMbeta2 (Mac-1, CD11b/CD18) and alphaDbeta2 (CD11d/CD18) in Macrophage Fusion. Am J Pathol 186(8):2105-16 |
| abstractText | The subfamily of beta2 integrins is implicated in macrophage fusion, a hallmark of chronic inflammation. Among beta2 family members, integrin Mac-1 (alphaMbeta2, CD11b/CD18) is abundantly expressed on monocyte/macrophages and mediates critical adhesive reactions of these cells. However, the role of Mac-1 in macrophage fusion leading to the formation of multinucleated giant cells remains unclear. Moreover, the role of integrin alphaDbeta2 (CD11d/CD18), a receptor with recognition specificity overlapping that of Mac-1, is unknown. We found that multinucleated giant cells are formed in the inflamed mouse peritoneum during the resolution phase of inflammation, and their numbers were approximately twofold higher in wild-type mice than in Mac-1(-/-) mice. Analyses of isolated inflammatory peritoneal macrophages showed that IL-4-induced fusion of Mac-1-deficient cells was strongly reduced compared with wild-type counterparts. The examination of adhesive reactions known to be required for fusion showed that spreading, but not adhesion and migration, was reduced in Mac-1-deficient macrophages. Fusion of alphaDbeta2-deficient macrophages was also significantly decreased, albeit to a smaller degree. Deficiency of intercellular adhesion molecule 1, a counter-receptor for Mac-1 and alphaDbeta2, did not alter the fusion rate. The results indicate that both Mac-1 and alphaDbeta2 support macrophage fusion with Mac-1 playing a dominant role and suggest that Mac-1 may mediate cell-cell interactions with a previously unrecognized counter-receptor(s). |
