Angiogenesis, the development and growth of new blood vessels, is important for organ development, wound healing and various pathological conditions such as tumor growth or proliferative retinopathies. Neovascularization depends on integrin-mediated adhesive contacts of the endothelial cells with the extracellular matrix as well as on the function of growth factors. There is emerging evidence that inflammatory cells, and particularly neutrophils, regulate endothelial cell functions related to angiogenesis. The participation of inflammatory cells in angiogenesis may depend on the biological context. Both pro-angiogenic and anti-angiogenic activities of neutrophils have been described. Neutrophils are a source of growth factors and proteases. However, neutrophil can generate the anti-angiogenic factors angiostatin and alpha-defensin. 1) We could show that alpha-defensins form a ternary complex with fibronectin (FN) and alpha5beta1-integrin and transform the FN-alpha5beta1-integrin interaction to one that does not promote endothelial cell adhesion. alpha-defensins thereby interfered with endothelial cell functions related to angiogenesis in vitro and in vivo. 2) The anti-angiogenic factor angiostatin was identified as a ligand of the leukocyte beta2-integrin Mac-1. Angiostatin was thereby found to exert an anti-inflammatory action by inhibiting leukocyte recruitment in vitro and in vivo.3) Developmentaly regulated endothelial locus-1 (Del-1) is thought to be an embryonic protein regulating developmental angiogenesis. However, Del-1 ko mice had normal angiogenesis. We have studied the expression of Del-1 in adult tissues and found it to be expressed in lungs and brain and to be upregulated under inflammation. The role of Del-1 as a leukocyte beta2-integrin ligand in inflammatory conditions of lung and brain is currently being evaluated.
