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

Daniel H. Madsen, Daniel Leonard, Andrius Masedunskas, Amanda Moyer, Henrik Jessen Jürgensen, Diane E. Peters, Panomwat Amornphimoltham, Arul Selvaraj, Susan S. Yamada, David A. Brenner, Sven Burgdorf, Lars H. Engelholm, Niels Behrendt, Kenn Holmbeck, Roberto Weigert, Thomas H. Bugge

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)951-966
Number of pages16
JournalJournal of Cell Biology
Issue number6
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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