Effect of Tyr AG490 and other chemokine inhibitors on lymphocyte chemotaxis to CCL21 and CXCL12.

Freshly isolated mouse lymphocytes were treated with inhibitors and allowed to migrate in a chemotaxis assay as described in “Materials and methods.” (A) Migration toward 100 nM CCL21. Data are pooled from 3-6 independent experiments and expressed as means ± SDs of percent control migration. (B) Migration toward 50 nM CXCL12. Data are pooled from 3-4 independent experiments. For panels A and B, Untr indicates untreated; PTX, pertussis toxin; CTX, cholera toxin; DM, DMSO; Ly, Ly294002; Wn, wortmannin; *P < .05 versus untreated (control). (C) Migration of control (DMSO)– and Tyr AG490–treated lymphocytes toward different CCL21 concentrations (n = 3-6). (D) Migration of control (DMSO)– and Tyr AG490–treated lymphocytes to 100 nM CCL19 (n = 3). All asterisks indicate P < .05. (E) Similar expression of adhesion molecules and CCR7 in control- and Tyr AG490–treated Thy1.2- and B220-positive cells. Flow cytometric analysis was carried out with mAbs as described in “Material and methods” and analyzed on a Coulter XL flow cytometer. For detection of CCR7 expression, CCL19-Ig was employed.