title: Mechanism of sphingosine 1-phosphate- and lysophosphatidic acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.
abstract: The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.
authors.affiliation: Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland; E-Mails: rcostello@rcsi.ie (R.W.C.); micmaloney@rcsi.ie (M.M.); matiyeh@rcsi.ie (M.A.).
authors.forename: Richard W
authors.initials: RW
authors.lastname: Costello
authors.forename: Michael
authors.initials: M
authors.lastname: Maloney
authors.forename: Mazin
authors.initials: M
authors.lastname: Atiyeh
authors.forename: Gerald
authors.initials: G
authors.lastname: Gleich
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Walsh
mesh_terms: D002460:Cell Line; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D015854:Up-Regulation
chemical_list: D002631:Chemotactic Factors, Eosinophil; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C032881:lysophosphatidic acid