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Macrophage fusion, giant cell formation, and the foreign body response require matrix metalloproteinase 9
Author(s) -
MacLauchlan Susan,
Skokos Eleni A.,
Meznarich Norman,
Zhu Dana H.,
Raoof Sana,
Shipley J. Michael,
Senior Robert M.,
Bornstein Paul,
Kyriakides Themis R.
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1008588
Subject(s) - foreign body giant cell , matrix metalloproteinase , macrophage , biology , giant cell , angiogenesis , microbiology and biotechnology , extracellular matrix , cell fusion , matrix (chemical analysis) , immunology , pathology , in vitro , cell , chemistry , biochemistry , cancer research , medicine , genetics , chromatography
Macrophages undergo fusion to form multinucleated giant cells in several pathologic conditions, including the foreign body response (FBR). We detected high levels of matrix metalloproteinase (MMP)‐9 during macrophage fusion in vitro and in foreign body giant cells (FBGCs) in vivo. Wild‐type (WT) bone marrow‐derived macrophages were induced to fuse with IL‐4 in the presence of MMP‐9 function‐blocking antibodies and displayed reduced fusion. A similar defect, characterized by delayed shape change and abnormal morphology, was observed in MMP‐9 null macrophages. Analysis of the FBR in MMP‐9 null mice was then pursued to evaluate the significance of these findings. Specifically, mixed cellulose ester disks and polyvinyl alcohol sponges were implanted s.c. in MMP‐9 null and WT mice and excised 2–4 weeks later. Histochemical and immunohistochemical analyses indicated equal macrophage recruitment between MMP‐9 null and WT mice, but FBGC formation was compromised in the former. In addition, MMP‐9 null mice displayed abnormalities in extracellular matrix assembly and angiogenesis. Consistent with a requirement for MMP‐9 in fusion, we also observed reduced MMP‐9 levels in MCP‐1 null macrophages, previously shown to be defective in FBGC formation. Collectively, our studies show abnormalities in MMP‐9 null mice during the FBR and suggest a role for MMP‐9 in macrophage fusion.