Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1991 Feb 1;273(Pt 3):573–578. doi: 10.1042/bj2730573

Metabolism of platelet-activating factor in human haematopoietic cell lines. Differences between myeloid and lymphoid cells.

M C Garcia 1, C Garcia 1, M A Gijon 1, S Fernandez-Gallardo 1, F Mollinedo 1, M Sanchez Crespo 1
PMCID: PMC1149801  PMID: 1847616

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.

Full text

PDF
573

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alonso F., Gil M. G., Sánchez-Crespo M., Mato J. M. Activation of 1-alkyl-2-lysoglycero-3-phosphocholine. Acetyl-CoA transferase during phagocytosis in human polymorphonuclear leukocytes. J Biol Chem. 1982 Apr 10;257(7):3376–3378. [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Benveniste J., Henson P. M., Cochrane C. G. Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. J Exp Med. 1972 Dec 1;136(6):1356–1377. doi: 10.1084/jem.136.6.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benveniste J., Tencé M., Varenne P., Bidault J., Boullet C., Polonsky J. Semi-synthèse et structure proposée du facteur activant les plaquettes (P.A.F.): PAF-acether, un alkyl ether analogue de la lysophosphatidylcholine. C R Seances Acad Sci D. 1979 Nov 26;289(14):1037–1040. [PubMed] [Google Scholar]
  5. Billah M. M., Eckel S., Myers R. F., Siegel M. I. Metabolism of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) by human promyelocytic leukemic HL60 cells. Stimulated expression of phospholipase A2 and acetyltransferase requires differentiation. J Biol Chem. 1986 May 5;261(13):5824–5831. [PubMed] [Google Scholar]
  6. Blank M. L., Lee T., Fitzgerald V., Snyder F. A specific acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid). J Biol Chem. 1981 Jan 10;256(1):175–178. [PubMed] [Google Scholar]
  7. Blank M. L., Snyder F., Byers L. W., Brooks B., Muirhead E. E. Antihypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochem Biophys Res Commun. 1979 Oct 29;90(4):1194–1200. doi: 10.1016/0006-291x(79)91163-x. [DOI] [PubMed] [Google Scholar]
  8. Blank M. L., Snyder F. Improved high-performance liquid chromatographic method for isolation of platelet-activating factor from other phospholipids. J Chromatogr. 1983 Apr 8;273(2):415–420. doi: 10.1016/s0378-4347(00)80963-9. [DOI] [PubMed] [Google Scholar]
  9. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  10. Camussi G., Bussolino F., Ghezzo F., Pegoraro L. Release of platelet-activating factor from HL-60 human leukemic cells following macrophage-like differentiation. Blood. 1982 Jan;59(1):16–22. [PubMed] [Google Scholar]
  11. Chilton F. H., Ellis J. M., Olson S. C., Wykle R. L. 1-O-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine. A common source of platelet-activating factor and arachidonate in human polymorphonuclear leukocytes. J Biol Chem. 1984 Oct 10;259(19):12014–12019. [PubMed] [Google Scholar]
  12. Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
  13. Collins S. J., Ruscetti F. W., Gallagher R. E., Gallo R. C. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci U S A. 1978 May;75(5):2458–2462. doi: 10.1073/pnas.75.5.2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Daniel L. W., Waite M., Wykle R. L. A novel mechanism of diglyceride formation. 12-O-tetradecanoylphorbol-13-acetate stimulates the cyclic breakdown and resynthesis of phosphatidylcholine. J Biol Chem. 1986 Jul 15;261(20):9128–9132. [PubMed] [Google Scholar]
  15. Demopoulos C. A., Pinckard R. N., Hanahan D. J. Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators). J Biol Chem. 1979 Oct 10;254(19):9355–9358. [PubMed] [Google Scholar]
  16. Dulioust A., Vivier E., Meslier N., Roubin R., Haye-Legrand I., Benveniste J. Biosynthesis of paf-acether. Paf-acether but not leukotriene C4 production is impaired in cultured macrophages. Biochem J. 1989 Oct 1;263(1):165–171. doi: 10.1042/bj2630165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dulioust A., Vivier E., Salem P., Benveniste J., Thomas Y. Immunoregulatory functions of paf-acether. I. Effect of paf-acether on CD4+ cell proliferation. J Immunol. 1988 Jan 1;140(1):240–245. [PubMed] [Google Scholar]
  18. Elstad M. R., Stafforini D. M., McIntyre T. M., Prescott S. M., Zimmerman G. A. Platelet-activating factor acetylhydrolase increases during macrophage differentiation. A novel mechanism that regulates accumulation of platelet-activating factor. J Biol Chem. 1989 May 25;264(15):8467–8470. [PubMed] [Google Scholar]
  19. Garcia M. C., Fernandez-Gallardo S., Gijon M. A., Garcia C., Nieto M. L., Sanchez Crespo M. Biosynthesis of platelet-activating factor (PAF) in human polymorphonuclear leucocytes. The role of lyso-PAF disposal and free arachidonic acid. Biochem J. 1990 May 15;268(1):91–98. doi: 10.1042/bj2680091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Homma H., Tokumura A., Hanahan D. J. Binding and internalization of platelet-activating factor 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine in washed rabbit platelets. J Biol Chem. 1987 Aug 5;262(22):10582–10587. [PubMed] [Google Scholar]
  21. Hwang S. B. Identification of a second putative receptor of platelet-activating factor from human polymorphonuclear leukocytes. J Biol Chem. 1988 Mar 5;263(7):3225–3233. [PubMed] [Google Scholar]
  22. Hwang S. B., Lee C. S., Cheah M. J., Shen T. Y. Specific receptor sites for 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) on rabbit platelet and guinea pig smooth muscle membranes. Biochemistry. 1983 Sep 27;22(20):4756–4763. doi: 10.1021/bi00289a022. [DOI] [PubMed] [Google Scholar]
  23. Kloprogge E., Akkerman J. W. Binding kinetics of PAF-acether (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) to intact human platelets. Biochem J. 1984 Nov 1;223(3):901–909. doi: 10.1042/bj2230901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lacal P., Pulido R., Sánchez-Madrid F., Mollinedo F. Intracellular location of T200 and Mo1 glycoproteins in human neutrophils. J Biol Chem. 1988 Jul 15;263(20):9946–9951. [PubMed] [Google Scholar]
  25. Majerus P. W., Lastra R. Fatty acid biosynthesis in human leukocytes. J Clin Invest. 1967 Oct;46(10):1596–1602. doi: 10.1172/JCI105651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maudsley D. J., Morris A. G. Rapid intracellular calcium changes in U937 monocyte cell line: transient increases in response to platelet-activating factor and chemotactic peptide but not interferon-gamma or lipopolysaccharide. Immunology. 1987 Jun;61(2):189–194. [PMC free article] [PubMed] [Google Scholar]
  27. Miller L. J., Schwarting R., Springer T. A. Regulated expression of the Mac-1, LFA-1, p150,95 glycoprotein family during leukocyte differentiation. J Immunol. 1986 Nov 1;137(9):2891–2900. [PubMed] [Google Scholar]
  28. Pai J. K., Siegel M. I., Egan R. W., Billah M. M. Phospholipase D catalyzes phospholipid metabolism in chemotactic peptide-stimulated HL-60 granulocytes. J Biol Chem. 1988 Sep 5;263(25):12472–12477. [PubMed] [Google Scholar]
  29. Rola-Pleszczynski M., Pignol B., Pouliot C., Braquet P. Inhibition of human lymphocyte proliferation and interleukin 2 production by platelet activating factor (PAF-acether): reversal by a specific antagonist, BN 52021. Biochem Biophys Res Commun. 1987 Feb 13;142(3):754–760. doi: 10.1016/0006-291x(87)91478-1. [DOI] [PubMed] [Google Scholar]
  30. Rosoff P. M., Savage N., Dinarello C. A. Interleukin-1 stimulates diacylglycerol production in T lymphocytes by a novel mechanism. Cell. 1988 Jul 1;54(1):73–81. doi: 10.1016/0092-8674(88)90181-x. [DOI] [PubMed] [Google Scholar]
  31. Roubin R., Mencia-Huerta J. M., Landes A., Benveniste J. Biosynthesis of platelet-activating factor (PAF-acether). IV. Impairment of acetyl-transferase activity in thioglycollate-elicited mouse macrophages. J Immunol. 1982 Aug;129(2):809–813. [PubMed] [Google Scholar]
  32. Rovera G., Santoli D., Damsky C. Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2779–2783. doi: 10.1073/pnas.76.6.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sun F. F., Chau L. Y., Spur B., Corey E. J., Lewis R. A., Austen K. F. Identification of a high affinity leukotriene C4-binding protein in rat liver cytosol as glutathione S-transferase. J Biol Chem. 1986 Jun 25;261(18):8540–8546. [PubMed] [Google Scholar]
  34. Travers J. B., Li Q., Kniss D. A., Fertel R. H. Identification of functional platelet-activating factor receptors in Raji lymphoblasts. J Immunol. 1989 Dec 1;143(11):3708–3713. [PubMed] [Google Scholar]
  35. Travers J. B., Sprecher H., Fertel R. H. The metabolism of platelet-activating factor in human T-lymphocytes. Biochim Biophys Acta. 1990 Feb 6;1042(2):193–197. doi: 10.1016/0005-2760(90)90007-k. [DOI] [PubMed] [Google Scholar]
  36. Vallari D. S., Austinhirst R., Snyder F. Development of specific functionally active receptors for platelet-activating factor in HL-60 cells following granulocytic differentiation. J Biol Chem. 1990 Mar 15;265(8):4261–4265. [PubMed] [Google Scholar]
  37. Valone F. H., Coles E., Reinhold V. R., Goetzl E. J. Specific binding of phospholipid platelet-activating factor by human platelets. J Immunol. 1982 Oct;129(4):1637–1641. [PubMed] [Google Scholar]
  38. Valone F. H. Identification of platelet-activating factor receptors in P388D1 murine macrophages. J Immunol. 1988 Apr 1;140(7):2389–2394. [PubMed] [Google Scholar]
  39. Ward S. G., Westwick J. Antagonism of the platelet activating factor-induced rise of the intracellular calcium ion concentration of U937 cells. Br J Pharmacol. 1988 Apr;93(4):769–774. doi: 10.1111/j.1476-5381.1988.tb11461.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wykle R. L., Malone B., Snyder F. Enzymatic synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a hypotensive and platelet-aggregating lipid. J Biol Chem. 1980 Nov 10;255(21):10256–10260. [PubMed] [Google Scholar]
  41. van den Bosch H., Aarsman A. J., van Deenen L. L. Isolation and properties of a phospholipase A1 activity from beef pancreas. Biochim Biophys Acta. 1974 May 29;348(2):197–209. doi: 10.1016/0005-2760(74)90231-8. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES