Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx.
@article{Dean2008MacrophagespecificM, title={Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx.}, author={Richard A. Dean and Jennifer H. Cox and Caroline L. Bellac and Alain Doucet and Amanda E Starr and Christopher M. Overall}, journal={Blood}, year={2008}, volume={112 8}, pages={ 3455-64 } }
Through the activity of macrophage-specific matrix metalloproteinase-12 (MMP-12), we found that macrophages dampen the lipopolysaccharide (LPS)-induced influx of polymorphonuclear leukocytes (PMNs)-thus providing a new mechanism for the termination of PMN recruitment in acute inflammation. MMP-12 specifically cleaves human ELR(+) CXC chemokines (CXCL1, -2, -3, -5, and -8) at E-LR, the critical receptor-binding motif or, for CXCL6, carboxyl-terminal to it. Murine (m) MMP-12 also cleaves mCXCL1…
233 Citations
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Biochemically characterized MT6-MMP, profiled its tissue inhibitor of metalloproteinase inhibitory spectrum, performed degradomics analyses, and screened 26 chemokines for cleavage using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry to indicate a role for clearance of apoptotic neutrophils.
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A functional contribution of stable MTs in the enhanced trafficking of MMP-9 extracellularly is demonstrated, and it is shown that heterogeneity exists in macrophage cell populations with respect to M MP-9 production.
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- BiologyCell reports
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- Biology, ChemistryThe Journal of Biological Chemistry
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- Biology, ChemistryThe Journal of Biological Chemistry
- 2011
This study reveals for the first time that MMPs activate the long amino-terminal chemokines CCL15 and CCL23 to potent forms that have potential to increase monocyte recruitment during inflammation.
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- Biology, MedicineNature Communications
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- Biology, MedicineInternational immunopharmacology
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