Neutrophil-derived cytokines involved in physiological and pathological angiogenesis

Increasing data from the literature point to a neutrophil-mediated role via cytokine production in several aspects of mammalian biology, including angiogenesis. In such regard, neutrophils have been shown to synthetize and release a number of molecules able to promote, directly or indirectly, the growth and migration of endothelial cells, in turn inducing the formation of new blood vessels from preexisting ones. Interestingly, neutrophil-derived cytokines can be involved either in physiological or in pathological angiogenesis, depending on either the functioning or dysregulation of sophisticated interplays among different cell types, extracellular matrix and soluble mediators within the microenvironment. Our review resumes the most interesting studies elucidating the role of neutrophil-derived cytokines in human physiological and pathological angiogenesis. When appropriate, supporting observations generated in animal models will be also mentioned. Particular emphasis will be given to VEGF and PK2/Bv8, rather than CXCL8/IL-8 and OSM. We will also discuss the potential role of neutrophil-derived cytokines such as FGF2, Ang1 and IL-17, whose roles in angiogenesis - albeit anticipated - remain to be elucidated.