Autotaxin (ATX) is an ectoenzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid and a close relative of sphingosine 1-phosphate. High endothelial venules (HEVs) produce and secrete ATX into the blood[3]. HA130 is a selective ATX inhibitor with an IC50 of 28 nM[3]. HA130 abolished the enhancing effect of ATX on TEM (transendothelial migration) and HA130 at 0.3 mM completely ablated the activity of ATX on TK1 uropod formation[3]. When injecting CFSE-labeled T cells together with HA130 i.v. into mice and then reinjecting the drug at 7 and 12 min, SLOs (secondary lymphoid organs) were sectioned and stained to reveal HEVs after 15 min[3]. The ratio of outside HEVs to inside HEVs was used as an index of T cell migration across HEVs. HA130 decreased the outside HEV/inside HEV ratio by 3–4-fold compared with vehicle treatment (p＜0.01 for both PLNs (peripheral lymph node) and MLNs (mesenteric lymph node)). This result is consistent with HA130 retarding the migration of T cells across LN (lymph node) HEVs[3]. The s.c. administration of HA130 induces marked lymphocyte accumulation within the endothelial cell (EC) and sub-EC layers of HEVs in draining lymph nodes[4].
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