Neutrophil-activating protein-2- and interleukin-8-mediated angiogenesis.

In this study, we investigated the anti-angiogenic potential of nitric oxide (NO) donors and anti-integrin compounds against neutrophil-activating protein-2 (NAP-2), interleukin-8 (IL-8), and basic fibroblast growth factor (FGF-2)-induced angiogenesis. In vivo, recombinant human NAP-2 and FGF-2 induce a potent and comparable angiogenic response in the chick embryo chorioallantoic membrane (CAM). We demonstrate that NO donors and anti-integrin agents are capable of abrogating either NAP-2- or FGF-2-induced angiogenesis in the CAM model. The NO donor, S-nitroso N-acetyl penicillamine (SNAP), blocked either NAP-2- or FGF-2-mediated angiogenesis in the CAM. Similarly, angiogenesis stimulated with NAP-2 or FGF-2 was blocked by antagonist of the alphavbeta3 integrin in the CAM model. However, the inhibition of NAP-2 and IL-8 by the anti-integrin compound is significantly less than the inhibition observed with FGF-2 as the angiogenic stimulus. Similarly, the ability of these mechanisms to also inhibit endothelial cell differentiation was demonstrated. Taken together, these data illustrate the involvement of multiple pathways in the mechanisms of action for the alpha-chemokine- and cytokine-mediated angiogenesis. These approaches may be a useful tool for the inhibition of angiogenesis associated with human tumor growth or with neovascular, ocular, and inflammatory diseases where chemokines and cytokines are involved.