Lysophospholipids and chemokines activate distinct signal transduction pathways in T helper 1 and T helper 2 cells.
We demonstrate the expression of S1P(1,3,4,5) the receptors for sphingosine 1-phosphate (S1P), and LPA(1,2,3) the receptors for lysophosphatidic acid (LPA) in T helper 1 (Th1) and T helper 2 (Th2) cells. S1P 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 eotaxin-induced Th2 cell chemotaxis are blocked by PTX pretreatment. LPA but not S1P 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 [Ca(2+)](i) release in Th1 and Th2 cells. Our results indicate that lysophospholipids and chemokines stimulate different signal transduction pathways.
Wang
Ling
L
Department of Anatomy, University of Oslo, POB 1105 Blindern, N-0317 Oslo, Norway.
Knudsen
Eirunn
E
Jin
Yixin
Y
Gessani
Sandra
S
Maghazachi
Azzam A
AA
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D054413:Chemokine CCL11; D054371:Chemokine CXCL11; D018925:Chemokines / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
C515456:CCL11 protein, human; C515202:CXCL11 protein, human; D054413:Chemokine CCL11; D054371:Chemokine CXCL11; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D049349:Receptors, Lysosphingolipid; D002118:Calcium