Lysophospholipids and chemokines activate distinct signal transduction pathways in T helper 1 and T helper 2 cells

We demonstrate the expression Of SIP1,3,4,5 the receptors for sphingosine I-phosphate (SIP), and LPA(1,2,3) the receptors for lysophosphatidic acid (LPA) in T helper I (Th1) and T helper 2 (Th2) cells. S I P and LPA induce the chemotaxis of Th1 and Th2 cells, an activity that is resistant to pertussis toxin (PTX) pretreatment in Th1, but is sensitive in Th2 cells. Also, I-TAC-induced Th1 and cotaxin-induced Th2 cell chemotaxis are blocked by PTX pretreatment. LPA but not S I P induces calcium flux response in Th1 and Th2 cells, which is due to the influx of extracellular calcium and is mediated by receptor activation, since EGTA and suramin (SUR) completely abrogate LPA-induced the release of calcium. No cross-desensitization is observed between thapsigargin (TG) and LPA in both cell types. PTX and SUR but not EGTA inhibit I-TAC- or eotaxin-induced [Ca2+](i) release in Th1 and Th2 cells. Our results indicate that lysophospholipids and chemokines stimulate different signal transduction pathways. (C) 2004 Elsevier Inc. All rights reserved.