Surface-bound matrix metalloproteinase-8 on macrophages: Contributions to macrophage pericellular proteolysis and migration through tissue barriers.
Surface-bound matrix metalloproteinase-8 on macrophages: Contributions to macrophage pericellular proteolysis and migration through tissue barriers.
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DOI：
10.14814/phy2.14778
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发表时间：
2021-03
影响因子：
2.5
通讯作者：
Owen CA
中科院分区：
文献类型：
--
作者：
Wang X;Zhang D;Fucci QA;Dollery CM;Owen CA
MMP-8与PMN上的表面结合的金属蛋白酶组织抑制剂-1（TIMP-1）结合，在与组织破坏相关的炎性疾病的发展过程中促进细胞周围蛋白水解。关于巨噬细胞中MMP-8的生物学知之甚少。我们检验了以下假设：（1）MMP-8和TIMP-1也在活化的巨噬细胞表面表达，（2）巨噬细胞表面结合的MMP-8促进TIMP-抗性的细胞周围蛋白水解和巨噬细胞通过组织屏障迁移，（3）MMP-8与巨噬细胞表面结合的TIMP-1结合。使用免疫染色、生物素标记和底物裂解方法测量人单核细胞衍生的巨噬细胞（MDM）和/或鼠巨噬细胞的表面MMP-8和TIMP-1水平。测量了野生型（WT）小鼠活化巨噬细胞上膜结合Mmp-8对TIMP的敏感性。比较了WT和Mmp-8 −/−巨噬细胞通过体外组织屏障模型的迁移，以及WT与Mmp-8 −/−无菌性腹膜炎小鼠中腹腔巨噬细胞的蓄积。比较了WT和Timp-1 −/−小鼠活化巨噬细胞上Mmp-8的表面水平。脂多糖和分化簇40配体增加MDM和/或鼠巨噬细胞上的表面MMP-8和/或TIMP-1染色和表面I型胶原酶活性。活化的Mmp-8 −/−巨噬细胞比活化的WT巨噬细胞降解更少的I型胶原。WT巨噬细胞上的表面I型胶原酶活性对Timp-1的抑制具有抗性。在患有无菌性急性腹膜炎的WT和Mmp-8 −/−小鼠中，腹膜巨噬细胞蓄积相似。然而，Mmp-8 −/−巨噬细胞通过组织屏障模型（特别是含有I型胶原的模型）的迁移效率低于WT细胞。活化的WT和Timp-1 −/−巨噬细胞具有相似的表面结合Mmp-8水平。MMP-8和TIMP-1在活化的人MDM和鼠巨噬细胞的表面上表达，但MMP-8不太可能与这些细胞上的表面结合的TIMP-1结合。表面结合MMP-8有助于TIMP-抗性单核细胞/巨噬细胞细胞周蛋白水解和巨噬细胞迁移通过含胶原的组织屏障。促炎介质诱导单核细胞和巨噬细胞表面基质金属蛋白酶-8（MMP-8）的表达。单核细胞和巨噬细胞上的表面结合MMP-8具有催化活性，但对金属蛋白酶-1组织抑制剂的抑制具有抗性。单核细胞和巨噬细胞上的表面结合MMP-8有助于这些细胞通过含有I型胶原的组织屏障迁移。
MMP‐8 binds to surface‐bound tissue inhibitor of metalloproteinase‐1 (TIMP‐1) on PMNs to promote pericellular proteolysis during the development of inflammatory diseases associated with tissue destruction. Little is known about the biology of MMP‐8 in macrophages. We tested the hypotheses that: (1) MMP‐8 and TIMP‐1 are also expressed on the surface of activated macrophages, (2) surface‐bound MMP‐8 on macrophages promotes TIMP‐resistant pericellular proteolysis and macrophage migration through tissue barriers, and (3) MMP‐8 binds to surface‐bound TIMP‐1 on macrophages. Surface MMP‐8 and TIMP‐1 levels were measured on human monocyte‐derived macrophages (MDM) and/or murine macrophages using immunostaining, biotin‐labeling, and substrate cleavage methods. The susceptibility of membrane‐bound Mmp‐8 on activated macrophages from wild‐type (WT) mice to TIMPs was measured. Migration of WT and Mmp‐8 −/− macrophages through models of tissue barriers in vitro and the accumulation of peritoneal macrophages in WT versus Mmp‐8 −/− mice with sterile peritonitis was compared. Surface levels of Mmp‐8 were compared on activated macrophages from WT and Timp‐1 −/− mice. Lipopolysaccharides and a cluster of differentiation 40 ligand increased surface MMP‐8 and/or TIMP‐1 staining and surface type I collagenase activity on MDM and/or murine macrophages. Activated Mmp‐8 −/− macrophages degraded less type I collagen than activated WT macrophages. The surface type‐I collagenase activity on WT macrophages was resistant to inhibition by Timp‐1. Peritoneal macrophage accumulation was similar in WT and Mmp‐8 −/− mice with sterile acute peritonitis. However, Mmp‐8 −/− macrophages migrated less efficiently through models of tissue barriers (especially those containing type I collagen) than WT cells. Activated WT and Timp‐1 −/− macrophages had similar surface‐bound Mmp‐8 levels. MMP‐8 and TIMP‐1 are expressed on the surface of activated human MDM and murine macrophages, but Mmp‐8 is unlikely to bind to surface‐bound Timp‐1 on these cells. Surface‐bound MMP‐8 contributes to TIMP‐resistant monocyte/macrophage pericellular proteolysis and macrophage migration through collagen‐containing tissue barriers. Pro‐inflammatory mediators induce the expressed of matrix metalloproteinase‐8 (MMP‐8) on the the surface of monocytes and macrophages. Surface‐bound MMP‐8 on monocytes and macrophages is catalytically active but resistant to inhibition by tissue inhibitor of metalloproteinases‐1. Surface‐bound MMP‐8 on monocytes and macrophages contributes to the migration of these cells through tissue barriers containing type‐I collagen.