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A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo

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Motley, MP, Madsen, DH, Jürgensen, HJ, Spencer, DE, Szabo, R, Holmbeck, K, Flick, MJ, Lawrence, DA, Castellino, FJ, Weigert, R & Bugge, TH 2016, 'A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo' Blood, bind 127, nr. 9, s. 1085-96. https://doi.org/10.1182/blood-2015-05-644260

APA

CBE

Motley MP, Madsen DH, Jürgensen HJ, Spencer DE, Szabo R, Holmbeck K, Flick MJ, Lawrence DA, Castellino FJ, Weigert R, Bugge TH. 2016. A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo. Blood. 127(9):1085-96. https://doi.org/10.1182/blood-2015-05-644260

MLA

Vancouver

Author

Motley, Michael P ; Madsen, Daniel H ; Jürgensen, Henrik J ; Spencer, David E ; Szabo, Roman ; Holmbeck, Kenn ; Flick, Matthew J ; Lawrence, Daniel A ; Castellino, Francis J ; Weigert, Roberto ; Bugge, Thomas H. / A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo. I: Blood. 2016 ; Bind 127, Nr. 9. s. 1085-96.

Bibtex

@article{4e0e0556570c48c68f0a18c7b8d9c7ce,
title = "A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo",
abstract = "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.",
keywords = "Animals, Biological Assay, Cell Proliferation, Endocytosis, Fibrin, Fibrinolysin, Macrophages, Mice, Myeloid Cells, Plasminogen, Plasminogen Activators, Proteolysis, Receptors, CCR2, Receptors, Chemokine, Receptors, Peptide, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Motley, {Michael P} and Madsen, {Daniel H} and J{\"u}rgensen, {Henrik J} and Spencer, {David E} and Roman Szabo and Kenn Holmbeck and Flick, {Matthew J} and Lawrence, {Daniel A} and Castellino, {Francis J} and Roberto Weigert and Bugge, {Thomas H}",
year = "2016",
month = "3",
day = "3",
doi = "10.1182/blood-2015-05-644260",
language = "English",
volume = "127",
pages = "1085--96",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

RIS

TY - JOUR

T1 - A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo

AU - Motley, Michael P

AU - Madsen, Daniel H

AU - Jürgensen, Henrik J

AU - Spencer, David E

AU - Szabo, Roman

AU - Holmbeck, Kenn

AU - Flick, Matthew J

AU - Lawrence, Daniel A

AU - Castellino, Francis J

AU - Weigert, Roberto

AU - Bugge, Thomas H

PY - 2016/3/3

Y1 - 2016/3/3

N2 - 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.

AB - 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.

KW - Animals

KW - Biological Assay

KW - Cell Proliferation

KW - Endocytosis

KW - Fibrin

KW - Fibrinolysin

KW - Macrophages

KW - Mice

KW - Myeloid Cells

KW - Plasminogen

KW - Plasminogen Activators

KW - Proteolysis

KW - Receptors, CCR2

KW - Receptors, Chemokine

KW - Receptors, Peptide

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1182/blood-2015-05-644260

DO - 10.1182/blood-2015-05-644260

M3 - Journal article

VL - 127

SP - 1085

EP - 1096

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -

ID: 49658701