Figure 1.
Role of RANTES oligomerization in RANTES-triggered leukocyte arrest and spreading in shear flow. Activated HMVECs were preincubated with wild-type RANTES or RANTES mutants, as indicated. The heparan sulfate–specific immobilization of RANTES or mutants on HMVECs was determined by subtracting the optical density after treatment of HMVECs with heparitinase I from that without heparitinase I (A). Monocytes stimulated with RANTES or mutants at 10 nM at 37°C were subjected to static adhesion on purified ICAM-1 for 15 minutes, and adhesion is given as percentage of input cells (B). Monocytes (C,E) or CD45RO+CD4+ T cells (D,F) pretreated with the CCR1 antagonist BX471, the CCR5 antagonist TAK-779, or dimethyl sulfoxide (0.1%) were perfused across activated HMVECs in a flow chamber at 1.5 dyne/cm2. After 5 minutes, firmly adherent cells per square millimeter were counted and expressed as percentage of control (without RANTES), and the percentage of cells undergoing spreading and/or transmigration among adherent cells was determined. Data represent mean ± SD of 6 separate experiments. *P < .05 versus wild-type RANTES (nonparametric signed-rank tests).