Surface‐bound matrix metalloproteinase‐8 on macrophages: Contributions to macrophage pericellular proteolysis and migration through tissue barriers

摘要: Objective MMP-8 binds to surface-bound tissue inhibitor of metalloproteinase-1 (TIMP-1) on PMNs promote pericellular proteolysis during the development inflammatory diseases associated with destruction. Little is known about biology in macrophages. We tested hypotheses that: (1) and TIMP-1 are also expressed surface activated macrophages, (2) macrophages promotes TIMP-resistant macrophage migration through barriers, (3) Methods Surface levels were measured human monocyte-derived (MDM) and/or murine using immunostaining, biotin-labeling, substrate cleavage methods. The susceptibility membrane-bound Mmp-8 from wild-type (WT) mice TIMPs was measured. Migration WT Mmp-8-/- models barriers vitro accumulation peritoneal versus sterile peritonitis compared. compared Timp-1-/- mice. Results Lipopolysaccharides a cluster differentiation 40 ligand increased staining type I collagenase activity MDM Activated degraded less collagen than type-I resistant inhibition by Timp-1. Peritoneal similar acute peritonitis. However, migrated efficiently (especially those containing collagen) cells. had levels. Conclusions but unlikely bind Timp-1 these Surface-bound contributes monocyte/macrophage collagen-containing barriers.