| First Author | Van Gassen N | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 5 | Pages | 1482-93 |
| PubMed ID | 25645754 | Mgi Jnum | J:229643 |
| Mgi Id | MGI:5752716 | Doi | 10.1002/eji.201445013 |
| Citation | Van Gassen N, et al. (2015) Macrophage dynamics are regulated by local macrophage proliferation and monocyte recruitment in injured pancreas. Eur J Immunol 45(5):1482-93 |
| abstractText | Pancreas injury by partial duct ligation (PDL) activates a healing response, encompassing beta-cell neogenesis and proliferation. Macrophages (MPhis) were recently shown to promote beta-cell proliferation after PDL, but they remain poorly characterized. We assessed myeloid cell diversity and the factors driving myeloid cell dynamics following acute pancreas injury by PDL. In naive and sham-operated pancreas, the myeloid cell compartment consisted mainly of two distinct tissue-resident MPhi types, designated MHC-II(lo) and MHC-II(hi) MPhis, the latter being predominant. MHC-II(lo) and MHC-II(hi) pancreas MPhis differed at the molecular level, with MHC-II(lo) MPhis being more M2-activated. After PDL, there was an early surge of Ly6C(hi) monocyte infiltration in the pancreas, followed by a transient MHC-II(lo) MPhi peak and ultimately a restoration of the MHC-II(hi) MPhi-dominated steady-state equilibrium. These intricate MPhi dynamics in PDL pancreas depended on monocyte recruitment by C-C chemokine receptor 2 and macrophage-colony stimulating factor receptor as well as on macrophage-colony stimulating factor receptor-dependent local MPhi proliferation. Functionally, MHC-II(lo) MPhis were more angiogenic. We further demonstrated that, at least in C-C chemokine receptor 2-KO mice, tissue MPhis, rather than Ly6C(hi) monocyte-derived MPhis, contributed to beta-cell proliferation. Together, our study fully characterizes the MPhi subsets in the pancreas and clarifies the complex dynamics of MPhis after PDL injury. |
