Altogether, these data demonstrate that MT1-MMP plays an important role during endothelial cell migration, and its activity can modulate endothelial migration, invasion, and formation of capillary tubes during the angiogenic response.

Mice chimeric for the expression of alpha4 integrins were used to dissect the roles of these receptors in development and traffic of lymphoid and myeloid cells. During fetal life, T cell development is alpha4 independent, but after birth further production of T cells becomes alpha4 dependent. Precursors for both T and B cells require alpha4 integrins for normal development within the bone marrow. In contrast, monocytes and natural killer cells can develop normally without alpha4 integrins. Thus, there are lymphocyte-specific, developmentally regulated requirements for alpha4 integrins in hematopoiesis in the bone marrow. We also show that alpha4 integrins are essential for T cell homing to Peyer's patches, but not to other secondary lymphoid organs, including spleen, lymph nodes, and intestinal epithelium.

Inflammation and angiogenesis are frequently coupled in pathological situations such as atherosclerosis, diabetes, and arthritis. The inflammatory response increases capillary permeability and induces endothelial activation, which, when persistent, results in capillary sprouting. This inflammation-induced angiogenesis and the subsequent remodelling steps are in large part mediated by extracellular matrix (ECM) proteins and proteases. The focal increase in capillary permeability is an early consequence of inflammation, and results in the deposition of a provisional fibrin matrix. Subsequently, ECM turnover by proteases permits an invasive program by specialized endothelial cells whose phenotype can be regulated by inflammatory stimuli. ECM activity also provides specific mechanical forces, exposes cryptic adhesion sites, and releases biologically active fragments (matrikines) and matrix-sequestered growth factors, all of which are critical for vascular morphogenesis. Further matrix remodelling and vascular regression contribute to the resolution of the inflammatory response and facilitate tissue repair.