title: Metabolism of platelet-activating factor in human haematopoietic cell lines. Differences between myeloid and lymphoid cells.
abstract: The binding and metabolism of platelet-activating factor (PAF) was studied in human cell lines resembling myeloid cells (HL60 and U937) and B and T lymphocytes (Daudi and Jurkat). All of the cell lines were found to bind and catabolize exogenous [3H]PAF in a time- and temperature-dependent manner. PAF binding could also be demonstrated in isolated membrane fractions, which provides further evidence of the existence of true membrane receptors. Myeloid cell lines contained numbers of receptors at least 10-fold higher than in lymphoid cell lines. Biosynthesis of PAF upon challenge by ionophore A23187 could be demonstrated in HL60 and U937 cells. In contrast, lymphoid cell lines were unable to produce PAF. Incubation with [14C]acetate showed incorporation of the label into three main fractions: neutral lipids, phosphatidylcholine and PAF, but the distribution of the label varied depending on the cell line. Significant incorporation into phosphatidylcholine was observed in uninduced myeloid cell lines. A phospholipase A2 acting on 1-O-hexadecyl-2-arachidonoyl-sn-glycero-3-phosphocholine and an acetyl-CoA:lyso-PAF acetyltransferase were expressed in the HL60 cell line and showed variations in specific activity with granulocytic differentiation. In contrast, these enzyme activities were not expressed in Daudi and Jurkat cell lines. These data indicate (1) the occurrence of PAF binding and catabolism in both myeloid and lymphoid cell lines; (2) the restriction of PAF biosynthesis to myeloid cell lines, especially HL60 cells; (3) the occurrence of differentiation-elicited changes in the specific activities of the enzymes involved in PAF biosynthesis by the remodelling pathway; and (4) the central role played by the disposal of lyso-PAF, a product of the phospholipase A2 reaction, in PAF biosynthesis.
authors.affiliation: Instituto de Investigaciones Médicas de la Fundación Jiménez Díaz, Centro Asociado al CSIC, Madrid, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Garcia
authors.forename: C
authors.initials: C
authors.lastname: Garcia
authors.forename: M A
authors.initials: MA
authors.lastname: Gijon
authors.forename: S
authors.initials: S
authors.lastname: Fernandez-Gallardo
authors.forename: F
authors.initials: F
authors.lastname: Mollinedo
authors.forename: M
authors.initials: M
authors.lastname: Sanchez Crespo
mesh_terms: D000085:Acetates / Q000378:metabolism; D000123:Acetyltransferases / Q000378:metabolism; D001402:B-Lymphocytes; D002051:Burkitt Lymphoma; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D016403:Lymphoma, Large B-Cell, Diffuse; D010743:Phospholipids / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D013463:Sulfuric Acid Esters / Q000494:pharmacology; D013601:T-Lymphocytes; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000085:Acetates; D010743:Phospholipids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013463:Sulfuric Acid Esters; C039351:platelet activating factor receptor; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; C007482:dimethyl sulfate; D013755:Tetradecanoylphorbol Acetate