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- _2 value "To determine the mechanism by which IL-18 mediates angiogenesis, we hypothesized that IL-18 may act through integrins present on HMVECs. TNF-a is angiogenic in part via its action on integrin avb3 (34). Thus, we examined whether blocking avb3 would inhibit IL-18-induced angiogenesis in the HMVEC migration assay. HMVECs were first incubated with anti-avb3 Ab or nonspecific control IgG at 25 mg/ml for 1 h before and during the chemotaxis assay. IL-18 (10 nM) was then used to stimulate HMVEC migration, and comparison was made with the control stimulants bFGF and TNF-a. To illustrate a contrasting mechanism, VEGF was also used as another stimulant, which would not be expected to be inhibited by blocking avb3, since the angiogenic ability of VEGF is thought to occur via the integrin avb5 (42). Blocking HMVEC avb3 resulted in significant inhibition of IL-18-induced cell migration comparable with that seen with control (Fig. 6). The same effect was seen with 25 or 10 mg/ml blocking Ab concentration. Significant inhibition of cell migration by blocking HMVEC avb3 before stimulation with bFGF and TNF-a was also demonstrated, while no change in cell migration occurred after stimulation with VEGF. Shown are the representative data from three separate assays." provenance.