title: Expression pattern analysis and activity determination of matrix metalloproteinase derived from human macrophage subsets.
abstract: The polarization behavior of macrophages determines the clinical outcome after implantation of biomaterials. Formation of classically activated macrophages (CAM) may result in cell fusion to form foreign body giant cells, which induce and support uncontrolled inflammatory responses and can cause undesired material degradation. In contrast, polarization into alternatively activated macrophages (AAM) is assumed to support healing processes and implant integration. The expression of matrix metalloproteinases (MMP) by the different macrophage subsets might play a crucial role for inflammatory and wound healing processes and may subsequently influence the implant integration. Therefore, it is of importance to characterize the MMP expression pattern by the different macrophage subsets. This knowledge could support the design of biomaterials in which specific MMP cleavage sites are incorporated allowing a controlled cell-mediated degradation of the material. However, it needs to be considered that the pure expression levels may not correlate with the enzymatic activity of the MMP, which depends on a variety of different parameters such as additional co-factors. For this reason, the differential MMP expression levels and the overall enzymatic activity of in vitro generated human non-polarized macrophages (M0), CAM, and AAM are analyzed in this study. While MMP-1, MMP-3, and MMP-10 showed the highest expression levels in CAM, MMP-12 was most strongly expressed by AAM. Interestingly, although various MMP were expressed at high levels in CAM, the enzymatic MMP activity was increased in supernatants of AAM cultures. The data presented here illustrate the importance to combine the measurement of MMP expression levels with the analysis of the enzymatic activity. The observed MMP-12 expression in combination with the higher enzymatic activity detected in AAM supernatants might motivate the design of biomaterials, whose structure could be modified by MMP-12 catalyzed reactions leading to interactive polymers.
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Teltow, Germany Helmholtz Virtual Institute - Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany.
authors.forename: Toralf
authors.initials: T
authors.lastname: Roch
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Teltow, Germany.
authors.forename: Oksana
authors.initials: O
authors.lastname: Akymenko
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Teltow, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Krüger
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Teltow, Germany Helmholtz Virtual Institute - Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Jung
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Teltow, Germany Helmholtz Virtual Institute - Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Teltow, Germany Helmholtz Virtual Institute - Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lendlein
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D002384:Catalysis; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D015743:Giant Cells, Foreign-Body; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000201:enzymology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010641:Phenotype; D011108:Polymers / Q000737:chemistry; D014945:Wound Healing
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D020782:Matrix Metalloproteinases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Biomaterials; macrophage polarization; matrix metalloproteinase