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

Objective: 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.

Atherosclerosis and proteinase activation.

Rapidly accumulating evidence points to the matrix metalloproteinases (MMPs) as major molecular mediators of arterial diseases. Findings from human pathological specimens, animals, and cell and molecular biology implicate matrix metalloproteinases in all stages of atherosclerosis including lesion initiation and progression and ultimately in plaque complication and triggering of thrombosis. The complex interactions within the proteolytic cascade allow multiple levels of control over these functions.

Neutrophil elastase in human atherosclerotic plaques: production by macrophages.

Background: Catabolism of the extracellular matrix (ECM) contributes to vascular remodeling in health and disease. Although metalloenzymes and cysteinyl proteinases have garnered much attention in this regard, the role of serine-dependent proteinases in vascular ECM degradation during atherogenesis remains unknown. We recently discovered the presence of the metalloproteinase MMP-8, traditionally associated only with neutrophils, in atheroma-related cells.