TY - JOUR

T1 - M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway

AU - Madsen, Daniel H

AU - Leonard, Daniel

AU - Masedunskas, Andrius

AU - Moyer, Amanda

AU - Jürgensen, Henrik Jessen

AU - Peters, Diane E

AU - Amornphimoltham, Panomwat

AU - Selvaraj, Arul

AU - Yamada, Susan S

AU - Brenner, David A

AU - Burgdorf, Sven

AU - Engelholm, Lars H

AU - Behrendt, Niels

AU - Holmbeck, Kenn

AU - Weigert, Roberto

AU - Bugge, Thomas H

PY - 2013/9/16

Y1 - 2013/9/16

N2 - Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase-dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process.

AB - Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase-dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process.

KW - Animals

KW - Apoptosis

KW - Blotting, Western

KW - Cell Proliferation

KW - Cells, Cultured

KW - Collagen

KW - Collagen Type I

KW - Endocytosis

KW - Female

KW - Fibroblasts

KW - Green Fluorescent Proteins

KW - Humans

KW - Immunoenzyme Techniques

KW - Lysosomes

KW - Macrophages

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, Transgenic

KW - RNA, Messenger

KW - Real-Time Polymerase Chain Reaction

KW - Receptors, Cell Surface

KW - Receptors, Chemokine

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

U2 - 10.1083/jcb.201301081

DO - 10.1083/jcb.201301081

M3 - Journal article

C2 - 24019537

VL - 202

SP - 951

EP - 966

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 6

ER -