IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways

Cell Mol Physiol 280: L1094–L1103, 2001.—Stimulation of microvascular endothelial cells with interleukin (IL)-8 leads to cytoskeletal reorganization, which is mediated by com-bined activation of the CXCR1 and the CXCR2. In the early phase actin stress fibers appear, followed by cortical actin accumulation and cell retraction leading to gap formation between cells. The early response (between 1 and 5 min) is inhibited by an antibody that blocks the CXCR1. The later phase (from about 5 to 60 min), which is associated with cell retraction, is prevented by anti-CXCR2 antibody. Further-more, anti-CXCR2, but not anti-CXCR1, antibody blocked IL-8-mediated haptotaxis of endothelial cells on collagen. The later phase of the IL-8-mediated actin response is inhib-ited by pertussis toxin, indicating that the CXCR2 couples to Gi. In contrast, the early phase is blocked by C3 botulinu