A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo
Research output: Contribution to journal › Journal article › Research › peer-review
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, αMβ2 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.
Original language | English |
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Journal | Blood |
Volume | 127 |
Issue number | 9 |
Pages (from-to) | 1085-1096 |
Number of pages | 12 |
ISSN | 0006-4971 |
DOIs | |
Publication status | Published - 2016 |
- Animals, Biological Assay, CX3C Chemokine Receptor 1, Cell Proliferation, Endocytosis, Fibrin/metabolism, Fibrinolysin/metabolism, Macrophages/metabolism, Mice, Myeloid Cells/metabolism, Plasminogen/metabolism, Plasminogen Activators/metabolism, Proteolysis, Receptors, CCR2/metabolism, Receptors, Chemokine/metabolism, Receptors, Peptide/metabolism
Research areas
ID: 201162792