Inhibition of fibronectin-activated migration of microvascular endothelial cells by interleukin-1alpha, tumour necrosis factor alpha and interferon gamma.

The effect of interferon gamma (IFN) and the inflammatory cytokines tumour necrosis factor alpha (TNF) and interleukin 1alpha (IL-1) on micro- and macrovascular endothelial cell (EC) proliferation and migration was analysed. Whereas both micro- and macrovascular EC were growth-inhibited in response to the aforementioned cytokines, only microvascular EC were sensitive to TNF, IL-1 and IFN as inhibitors of fibronectin-activated cell migration. In addition, because microvascular EC play a crucial role in angiogenesis, and the formation of new capillaries depends upon the presence of angiogenic polypeptides, we evaluated the synthesis of fibroblast growth factor (FGF) type 1 and 2, Vascular Endothelial Growth Factor (VEGF) and Hepatocyte Growth Factor (HGF) in our system. Both micro- and macrovascular EC produce large amounts of FGF-2, which is mainly localized in the nucleus, and almost undetectable levels of FGF-1. In addition, the two cell types synthesize notable levels of VEGF and no HGF. Whether these findings are relevant to the different in vivo functions of EC residing different districts remains the focus of additional studies.