Role of plasminogen, plasmin, and plasminogen activators in the migration of fibroblasts into plasma clots

Abstract

Human diploid fibroblasts were seeded onto or into plasma clots and different aspects of cell adhesion and migration were measured. The roles of plasminogen activators and plasmin were studied by either the removal of plasminogen from plasma prior to clotting or by the addition of 10 mM epsilon-aminocaproic acid, which brings about an inhibition of plasmin in this system. When cells were seeded onto the surface of plasma clots, rates of attachment, spreading, and migration were unaffected by plasminogen depletion or plasmin inhibition. In contrast, when cells were seeded into plasma clots, then, although the rates of cells spreading were unaffected, cell migration was abolished by plasminogen depletion or by plasmin inhibition. When cells were seeded onto the surface of plasma clots and the rate of migration into the clots was measured, there was an absolute requirement for plasmin activity; while fibroblasts migrated rapidly into the fibrin lattice of control clots, in the case of plasminogen-depleted clots, cells failed to penetrate the lattice. Focussing through a plasma clot revealed that fibroblasts do not migrate through the fibrin lattice but instead, localized areas of fibrinolysis are generated and cells migrate over the surface of the area of lysis.

Tissue origin and extracellular matrix control neutral proteinase activity in human fibroblast three-dimensional cultures

“…Similar observations were reported in fibrin clots by Knox et al (1987). These vacuoles seemed more numerous in the case of gingival fibroblast cultures.…”

Mechanobiology in the Third Dimension

“…167,189 Furthermore, it forms a useful matrix into which fusion proteins (such as growth factors) can be attached to the matrix via the clotting transglutaminase factor XIIIa. 168 Cells must proteolytically degrade the dense fibrin mesh by releasing plasmin activators or MMPs (matrix metalloproteinases) in order to successfully migrate; 97,117,162 thus, fibrin is a useful matrix to study protease-dependent cell migration. The structural architectures of typical in vitro gels made of type I collagen and fibrin as seen by confocal reflectance microscopy are shown in Fig.…”

Effects of fibrinolysis on neurite growth from dorsal root ganglia cultured in two- and three-dimensional fibrin gels

“…The number of neurites that traverse the gap can be increased by adding fibrinogen-containing blood plasma, which changes the structure of the fibrin in the nerve gap (Williams, 1987;Williams et al, 1987). Finally, the addition of plasminogen affects the invasion of fibrin matrices by melanoma cells (Meissauer et al, 1992) and the migration of fibroblasts within fibrin clots (Knox et al, 1987).…”