Matrix metalloproteinases (MMPs) form a family of enzymes with major actions in the remodeling of extracellular matrix (ECM) components. Gelatinase B (MMP-9) is the most complex family member in terms of domain structure and regulation of its activity. Gelatinase B activity is under strict control at various levels: transcription of the gene by cytokines and cellular interactions; activation of...

Human umbilical vein endothelial cells (HUVECs) were used to gain insight into the molecular mechanism whereby the major extracellular protease from group A streptococci damages host tissue. HUVECs exposed to streptococcal cysteine protease (SCP) for various times exhibited cytopathic effect and cell detachment from the culture vessel. Gelatin substrate zymography showed that a time- and concen...

The ability of normal rabbit dermal fibroblasts to degrade films of type IV collagen and gelatin when stimulated by phorbol ester was shown to be dependent on the induction, secretion and activation of 95 kDa gelatinase B and the secretion and activation of 72 kDa gelatinase A and stromelysin. Degradation was inhibited by exogenous human recombinant tissue inhibitor of metalloproteinases-1, spe...

Our prior work shows that cultured BR cells derived from dog mastocytomas secrete the 92-kDa proenzyme form of gelatinase B. We provided a possible link between mast cell activation and metalloproteinase-mediated matrix degradation by demonstrating that alpha-chymase, a serine protease released from secretory granules by degranulating mast cells, converts progelatinase B to an enzymatically act...

Differentiation and maturation of myeloid cells is characterized by the sequential acquisition of two distinct cytoplasmic granule subsets, azurophil granules and specific granules. We recently showed the existence of a third granule subset, gelatinase granules. To investigate whether appearance of gelatinase granules marks a further step in maturation of myeloid cells beyond the appearance of ...

Matrix proteolysis is thought to play a crucial role in several stages of tumor progression, including angiogenesis, and the invasion and metastasis of tumor cells. We investigated the specific role of gelatinase A (matrix metalloproteinase 2) on these events using gelatinase A-deficient mice. In these mice, tumor-induced angiogenesis was suppressed according to dorsal air sac assay. When B16-B...

T cell extravasation from the bloodstream into the perivascular tissue during inflammation involves transmigration through the endothelial cell layer and basement membrane into the interstitial matrix. The specific mechanisms by which T cells transmigrate, however, are poorly understood. Matrix degradation by enzymes such as 72-kD gelatinase has been implicated as an important component in tiss...

Components involved in superoxide anion production (cytochrome b) and in cell adhesion processes (CD11b, CD11c, CD18), two early functional responses of neutrophils during acute inflammation, are intracellularly located in resting human neutrophils. We have found a correlation between secretion of gelatinase and overexpression in the plasma membrane of CD11b, CD11c, CD18 and cytochrome b upon c...

BACKGROUND AND PURPOSE Perivascularly positioned cerebral mast cells (MC) have been shown to participate in acute blood-brain barrier disruption and expansive brain edema following experimental transient cerebral ischemia. However, the underlying molecular mechanisms remain unknown. Because proteolytic gelatinase enzymes, matrix metalloproteinases (MMP)-2 and MMP-9, are thought to have a centra...