Roles of CCR1 and CCR5 in leukocyte recruitment.

Leukocytes were preincubated with CCR5 mAb or IgG2a isotype control (10 μg/mL), CCR1 antagonist BX471,13 CCR5 antagonist TAK-779 at 10 μM in flow assays or at 100 nM in chemotaxis assays, or DMSO (0.1% vol/vol). Monocytes (panels A, D), T_H1-cells (clone 305, panels B, E), or CD45RO⁺CD4⁺ memory T cells (panels C, F) were perfused on IL-1β–activated HMVECs left untreated (open bars) or pretreated with RANTES (solid bars) in a flow chamber at 1.5 dyne/cm². After 5 minutes, firmly adherent cells were counted and expressed as cells per square millimeter (panels A-C). Cells undergoing shape change were analyzed and expressed as a percentage of adherent cells (panels D-F). Data represent mean ± SD of 6 to 8 separate experiments. * indicates P < .05 vs RANTES control (nonparametric signed-rank tests). Both CCR1 and CCR5 mediate transendothelial chemotaxis of leukocytes. Monocytes (panel G), T_H1-cells (panel H), or CD45RO⁺CD4⁺ memory T cells (panel I) were subjected to chemotaxis assays for 90 minutes with RANTES (100 ng/mL) in the lower chamber. Transmigrated cells were counted by FACS and expressed as a percentage of input (panels G-I). DMSO or IgG2a had no effect. Data are mean ± SD of 4 to 6 separate experiments.