title: Cell-cell interaction between platelets and IL-1 beta-stimulated vascular smooth muscle cells in synthesis of thromboxane A2.
abstract: Transcellular biosynthesis of thromboxane (Tx) A2 between vascular smooth muscle cells (SMC) and platelets has been investigated by using 14C-arachidonic acid (AA) radiolabeled rat SMC (or platelets) and the fate of the label in phospholipids and eicosanoid fractions was studied using radioimmunoassay (RIA) and thin-layer chromatography (TLC). Stimulation of SMC with interleukin-1 beta (IL-1 beta) resulted in production of cyclooxygenase metabolites (e.g. 6-keto-PGF1 alpha, PGE2, PGF2 alpha, PGD2), 15-, 11-, 5-HETE, and free AA1 with a coincident decline of phosphatidylcholine (PC) in SMC. IL-1 beta did not induce TXB2 production, a stable metabolite of TXA2 measured by TLC and radioimmunoassay, either in human platelets from 0.01-100 U/ml for 1 h or in SMC for 24 h. However, human platelets converted exogenous PGH2 to TXA2 despite cyclooxygenase inhibition or PGH2 receptor blockade. Furthermore, TXB2 was produced in large quantities during co-incubation of IL-1 beta-stimulated SMC with human platelets for 30 min in concert with a significant decrease of 6-keto-PGF1 alpha and eicosanoids (PGE2, PGF2 alpha and PGD2) compared with control (P < 0.01). Pretreatment of SMC with cycloheximide and actinomycin not only inhibited IL-1 beta-induced eicosanoid synthesis and phospholipid breakdown but also diminished TXB2 production when co-incubated with platelets. These data suggest that a cell-cell interaction, i.e. platelet utilizing SMC-derived endoperoxides for its TXA2 production, might cause an excess thromboxane A2 synthesis.
authors.affiliation: Institut Biomedical des Cordeliers, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Zou
authors.forename: C
authors.initials: C
authors.lastname: Anges
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011449:Prostaglandin Endoperoxides / Q000378:metabolism; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D010743:Phospholipids; D011449:Prostaglandin Endoperoxides; D011463:Prostaglandins H; D011994:Recombinant Proteins; D003609:Dactinomycin; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D003513:Cycloheximide; D013917:Thrombin; D001241:Aspirin