Sphingosine 1-phosphate inhibits migration of RBL-2H3 cells via S1P2: cross-talk between platelets and mast cells.
To analyze the involvement in allergic reactions of platelets and sphingosine 1-phosphate (Sph-1-P), a lysophospholipid mediator released from activated platelets, the effects of Sph-1-P and a supernatant prepared from activated platelets on mast cell line RBL-2H3 were examined. Sph-1-P strongly inhibited the migration of both non-stimulated and fibronectin-stimulated RBL-2H3 cells, which was reversed by JTE-013, a specific antagonist of G protein-coupled Sph-1-P receptor S1P(2); S1P(2) was confirmed to be expressed in these cells. A similar anti-motility effect of Sph-1-P was observed in a phagokinetic assay. Consistent with these results, treatment of RBL-2H3 cells with Sph-1-P resulted in a rounded cell morphology, which was blocked by JTE-013. Under the present conditions, Sph-1-P failed to induce intracellular Ca(2+) mobilization or histamine degranulation, responses postulated to be elicited by intracellular Sph-1-P. Importantly, the Sph-1-P effect, i.e., the regulation of RBL-2H3 cell motility, was mimicked by the supernatant (both with and without boiling) prepared from activated platelets, and this effect of the supernatant was also blocked by JTE-013. Our results suggest that the motility of mast cells can be regulated by Sph-1-P and also platelets (which release Sph-1-P), via cell surface receptor S1P(2) (not through intracellular Sph-1-P actions, postulated previously in the same cells).
Yokoo
Eiko
E
Departments of Otolaryngology and Laboratory Medicine, University of Yamanashi Faculty of Medicine, 1110 Tamaho, Nakakoma, Yamanashi 409-3898, Japan.
Yatomi
Yutaka
Y
Takafuta
Toshiro
T
Osada
Makoto
M
Okamoto
Yoshitaka
Y
Ozaki
Yukio
Y
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015539:Platelet Activation; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*
C471998:JTE 013; D008246:Lysophospholipids; D011720:Pyrazoles; D011725:Pyridines; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine