Regulatory effect of lysophosphatidic acid on lymphocyte migration.
Lysophosphatidic acid (LPA) is a lipid mediator that is known to exhibit chemotactic activity toward a variety of cancer cells. However, its effect on the immune system has not been studied extensively. Another lipid mediator, sphingosine-1-phosphate (S1P), has been shown to influence lymphocyte recirculation by regulating lymphocyte egress from lymphoid organs. In this study, we found that LPA inhibits spontaneous migration of mouse splenic lymphocytes through a chemorepulsive effect. We also demonstrated that LPA inhibits chemokine CCL21-induced lymphocyte migration. This inhibitory effect on CCL21-induced migration was observed for both T and B cells. The involvement of a receptor, LPA(1), LPA(2) or LPA(3), in the inhibition of the CCL21-induced migration was confirmed with a synthetic agonist, oleyl thiophosphate. Considering that the signaling by CCL21 through cognate receptor CCR7 contributes to lymphocyte homing and dendritic cell trafficking to lymph nodes, LPA may play a role as a key regulator of these processes. The inhibitory effect of LPA is in remarkable contrast to the effect of S1P receptor signaling, which is known to potentiate lymphocyte chemotaxis involving CCR7.
Tanikawa
Takashi
T
Laboratory of Microbiology and Immunology and the Global COE Program, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan.
Kurohane
Kohta
K
Imai
Yasuyuki
Y
D000818:Animals; D002464:Cell Migration Inhibition / Q000187:drug effects / Q000276:immunology; D054421:Chemokine CCL21 / Q000037:antagonists & inhibitors / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D005233:Fatty Alcohols / Q000494:pharmacology; D005260:Female; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008246:Lysophospholipids / Q000819:agonists / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010755:Organophosphates / Q000494:pharmacology
D054421:Chemokine CCL21; D005233:Fatty Alcohols; D008246:Lysophospholipids; D010755:Organophosphates; C502989:oleoyl thiophosphate; C032881:lysophosphatidic acid