Arterioscler Thromb Vasc Biol CXCR2 Blockade Impairs Angiotensin II–Induced CC Chemokine Synthesis and Mononuclear Leukocyte Infiltration by Yafa Naim Abu Nabah, Mercedes Losada, Rossana Estellés, Teresa Mateo, Chantal Company, Laura Piqueras, Concha Lopez-Gines, Henry Sarau, Julio Cortijo, Esteban J. Morcillo, Peter J. Jose, and Maria-Jesus Sanz Arterioscler Thromb Vasc Biol Volume 27(11):2370-2376 November 1, 2007 Copyright © American Heart Association, Inc. All rights reserved.

Figure 1. Effects of SB-517785-M on Ang-II–induced leukocyte accumulation (A, B); chemokine mRNA expression (C) generation of CXC (D, E) and CC chemokines (F, G, H) in the rat peritoneal cavity. Figure 1. Effects of SB-517785-M on Ang-II–induced leukocyte accumulation (A, B); chemokine mRNA expression (C) generation of CXC (D, E) and CC chemokines (F, G, H) in the rat peritoneal cavity. Mean±SEM for n=4 to 8 animals, *P<0.05 or **P<0.01 relative to the PBS group; +P<0.05 or ++P<0.01 relative to the Ang-II group. Yafa Naim Abu Nabah et al. Arterioscler Thromb Vasc Biol. 2007;27:2370-2376 Copyright © American Heart Association, Inc. All rights reserved.

Figure 2. Effects of losartan, PD123,319, and a CXCR2 antagonist on subacute (4 hour) Ang-II–induced arteriolar leukocyte adhesion (A) venular leukocyte rolling flux (B), velocity (C), adhesion (D), and emigration (E) within rat mesenteric microvessels. Figure 2. Effects of losartan, PD123,319, and a CXCR2 antagonist on subacute (4 hour) Ang-II–induced arteriolar leukocyte adhesion (A) venular leukocyte rolling flux (B), velocity (C), adhesion (D), and emigration (E) within rat mesenteric microvessels. Results are mean±SEM for n=4 to 9 animals per group. **P<0.01 relative to the Buffer group; ++P<0.01 relative to the Ang-II group. Yafa Naim Abu Nabah et al. Arterioscler Thromb Vasc Biol. 2007;27:2370-2376 Copyright © American Heart Association, Inc. All rights reserved.

Figure 3. Effect of Ang-II and cold IL-8 of [125I]-IL-8 binding to human CXCR2-CHO cell membranes (A), CXCR2 mRNA (A), and protein expression (B). Figure 3. Effect of Ang-II and cold IL-8 of [125I]-IL-8 binding to human CXCR2-CHO cell membranes (A), CXCR2 mRNA (A), and protein expression (B). Results are mean±SEM of n=3 to 4 experiments: *P<0.05 relative to values in the medium group. +P<0.05 relative to 1 μmol/L Ang-II. Yafa Naim Abu Nabah et al. Arterioscler Thromb Vasc Biol. 2007;27:2370-2376 Copyright © American Heart Association, Inc. All rights reserved.

Figure 4. Effects of anti-CXCR1 and anti-CXCR2 mAbs on Ang-II–induced chemokine release (A, B), mononuclear cell arrest (C), and IL-8–induced MCP-1 release (D) from HUAECs. Results are mean±SEM of n=4 to 6 experiments: *P<0.05 or **P<0.01 relative to values in the medium group; +P<0.05 or ++P<0.01 relative to the stimulus group. Figure 4. Effects of anti-CXCR1 and anti-CXCR2 mAbs on Ang-II–induced chemokine release (A, B), mononuclear cell arrest (C), and IL-8–induced MCP-1 release (D) from HUAECs. Results are mean±SEM of n=4 to 6 experiments: *P<0.05 or **P<0.01 relative to values in the medium group; +P<0.05 or ++P<0.01 relative to the stimulus group. Yafa Naim Abu Nabah et al. Arterioscler Thromb Vasc Biol. 2007;27:2370-2376 Copyright © American Heart Association, Inc. All rights reserved.