| First Author | Motley MP | Year | 2016 |
| Journal | Blood | Volume | 127 |
| Issue | 9 | Pages | 1085-96 |
| PubMed ID | 26647393 | Mgi Jnum | J:232502 |
| Mgi Id | MGI:5779457 | Doi | 10.1182/blood-2015-05-644260 |
| Citation | Motley MP, et al. (2016) A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo. Blood 127(9):1085-96 |
| abstractText | Extravascular fibrin deposition accompanies many human diseases and causes chronic inflammation and organ damage, unless removed in a timely manner. Here, we used intravital microscopy to investigate how fibrin is removed from extravascular space. Fibrin placed into the dermis of mice underwent cellular endocytosis and lysosomal targeting, revealing a novel intracellular pathway for extravascular fibrin degradation. A C-C chemokine receptor type 2 (CCR2)-positive macrophage subpopulation constituted the majority of fibrin-uptaking cells. Consequently, cellular fibrin uptake was diminished by elimination of CCR2-expressing cells. The CCR2-positive macrophage subtype was different from collagen-internalizing M2-like macrophages. Cellular fibrin uptake was strictly dependent on plasminogen and plasminogen activator. Surprisingly, however, fibrin endocytosis was unimpeded by the absence of the fibrin(ogen) receptors, alphaMbeta2 and ICAM-1, the myeloid cell integrin-binding site on fibrin or the endocytic collagen receptor, the mannose receptor. The study identifies a novel fibrin endocytic pathway engaged in extravascular fibrin clearance and shows that interstitial fibrin and collagen are cleared by different subsets of macrophages employing distinct molecular pathways. |
