Advertisement

Interactions of Platelet Activating Factor and Prostaglandins in the Glomerulus and in Mesangial Cells

  • Detlef Schlondorff
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 259)

Abstract

Platelet activating factor (PAF) has been recognized as a potent mediator of inflammation and identified as l-alkyl-2-acetyl-sn-glycero-3-phospho-choline (Fig. 1). For biological activity, PAF requires an alkyl chain linked by an ether bond at the sn-1 position (most commonly a C16 length saturated chain) and an acetyl group at the sn-2 position. Loss of the acetyl group yielding lyso-PAF is associated with loss of biological activity (1–3). Many inflammatory cells have the capability to produce PAF upon stimulation, including peripheral leucocytes, with the exception of lymphocytes (1). Furthermore, cultured endothelial cells and renal cells (see below) can generate PAF. Stimuli that result in PAF formation cause an increase in intracellular calcium and include calcium ionophore, receptor-mediated phagocytosis or endocytosis, complement component C5a , formyl — methionyl — leucyl — phenyl — alanine and endotoxin (1–3). In general, resting cells do not produce PAF but require prior stimulation. Upon stimulation, PAF formation occurs via deacylation by phospholipase A2 of the precursor molecule l-alkyl-2-acyl-sn-glycero-3-phosphocholine to yield lyso PAF (Fig. 2). Lyso PAF is subsequently acetylated in position 2 by a specific acetyl-coenzyme A transferase to yield the active PAF molecule (1).

Keywords

Mesangial Cell Pertussis Toxin Glyceryl Ether Gial Cell Nephrotoxic Serum Nephritis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    F. Snyder, Chemical and biochemical aspects of platelet activating factor: a novel class of acetylated ether-linked choline-phospholipids, Med. Res. Rev. 5:107–140 (1985).PubMedCrossRefGoogle Scholar
  2. 2.
    R.N. Pinckard, L.M. McManus, D.J. Hanahan, Chemistry and biology of acetyl glyceryl ether phosphorylcholine (platelet-activating factor) , Adv. Inflamm. Res. 4:147–180 (1982).Google Scholar
  3. 3.
    B.B. Vargaftig, M. Chignard, J. Benveniste, J. Lefort, F. Wal, Background and present status of research on platelet-activating factor (PAF-acether), Ann. NY Acad. Sci. 370:119–137 (1981).PubMedCrossRefGoogle Scholar
  4. 4.
    F.H. Chilton, J.M. Ellis, S.C. Olson, R.L. Wykle, 0-Alkyl-2:sn-glycero-3-phosphocholine. A common source of platelet-activating factor and arachidonate in human polymorphonuclear leukocytes, J. Biol. Chem. 257:5402–5407 (1982).PubMedGoogle Scholar
  5. 5.
    D. Schlondorff and R. Neuwirth, Platelet-activating factor and the kidney, Am. J. Phvsiol. 251:F1–F11 (1986).Google Scholar
  6. 6.
    R.L. Hebert, P. Sirois, P. Braquet, G.E. Plante, Hemodynamic effects of PAF-acether on the dog kidney, Prostaglandins. Leukotrienes and Med. 26:189–202 (1987).CrossRefGoogle Scholar
  7. 7.
    H. Scherf, A.S. Nies, U. Schwertschlag, M. Hughes, J.G. Gerber, Hemodynamic effects of platelet-activating factor in the dog kidney in vivo, Hypertension 8:737–741 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    U. Schwertschlag, H. Scherf, J.G. Gerber, M. Mathias, A.S. Nies, L-platelet-activating factor (L-PAF) induces changes on renal vascular resistance, vascular reactivity and renin release in the isolated perfused rat kidney, Circulation Res. 60:534–539 (1987).PubMedCrossRefGoogle Scholar
  9. 9.
    U.S. Schwertschlag and V.W. Dennis, Renal hemodynamic and functional effects of platelet-activating factor, Clin. Res. 34:608A (1986).Google Scholar
  10. 10.
    S.M. Weisman, D. Felsen, E.D. Vaughan, Platelet-activating factor is a potent stimulus for renal prostaglandin synthesis: possible significance in unilateral ureteral ligation, J. Pharmacol. Exp. Ther. 235: 10–15 (1985).PubMedGoogle Scholar
  11. 11.
    E. Pirotzky, C. Page, J. Morley, J. Bidault, J. Benveniste, Vascular permeability induced by PAF-acether (platelet-activating factor) in the isolated perfused rat kidney, Agents Actions 16:1–2 (1985).CrossRefGoogle Scholar
  12. 12.
    G. Camussi, C. Tetta, R. Coda, G.P. Segoloni, A. Vercellone, Plateletactivating factor-induced loss of glomerular anionic charges, Kidney Int. 25:73–81 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    G. Camussi, Potential role of platelet-activating factor in renal pathophysiology, Kidney Int. 29:469–477 (1986).PubMedCrossRefGoogle Scholar
  14. 14.
    T. Bertani, M. Livio, D. Macconi, M. Mongi, G. Bisogno, C. Patrono, G. Remuzzi, Platelet-activating factor (PAF) as a mediator of injury in nephrotoxic nephritis, Kidney International 31:1248–1256 (1987).PubMedCrossRefGoogle Scholar
  15. 15.
    Z. Hruby, R.P. Lowry, R.D.C. Forbes, D. Blais, Immune reactivity and immunosuppressive intervention in experimental nephritis. IV. Effects of PAF (AGEPC) inhibitor CV3988 on albuminuria and histopathology in the accelerated autologous form of nephrotoxic serum nephritis, in: “Proceedings of the First Sandoz Research Symposium. New Horizons in Platelet-Activating Factor Research.” C.M. Winslow, ed., Wiley, London (1986).Google Scholar
  16. 16.
    G. Camussi, C. Tetta, C. Deregitus, F. Bussolino, G. Segolomi, A. Vercellone, Platelet-activating factor (PAF) in experimentally-induced rabbit acute serum sickness: role of basophil-derived PAF in immune complex deposition, J. Immunol. 128:86–94 (1982).PubMedGoogle Scholar
  17. 17.
    G. Camussi, I. Pawlowski, R. Saunders, J. Brentjens, G. Andres, A receptor antagonist of platelet-activating factor inhibits inflammatory injury induced by in situ formation of immune complexes in renal glomeruli and in skin, Lab. Invest. in press.Google Scholar
  18. 18.
    J. Wang and M.J. Dunn, Platelet-activating factor mediates endotoxininduced acute renal insufficiency in rats, Am. J. Physiol. 253 (Renal Fluid Electrolyte Physiol. 22):F1283–F1289, 1987.PubMedGoogle Scholar
  19. 19.
    J. Wang, M. Kester, M.J. Dunn, Endotoxin stimulates platelet-activating factor synthesis in cultured rat glomerular mesangial cells, Clin. Res. 35:638A (1987).Google Scholar
  20. 20.
    E. Pirotzky, J. Bidault, C. Burtin, M.C. Gubler, J. Benveniste, Release of platelet-activating factor, slow reacting substance and vasoactive species from isolated rat kidneys, Kidney Int. 25:404–410 (1984).PubMedCrossRefGoogle Scholar
  21. 21.
    E. Pirotzky, E. Ninio, J. Bidault, P. Pfister, J. Benveniste, Biosynthesis of platelet-activating factor. VI. Precursor of platelet-activating factor and acetyl transferase activity in isolated rat kidney cells, Lab. Invest. 51:567–572 (1984).PubMedGoogle Scholar
  22. 22.
    D. Schlondorff, P. Goldwasser, R. Neuwirth, J.A. Satriano, K. Clay, Production of platelet-activating factor in glomeruli and cultured glomerular mesangial cells, Am. J. Physiol. 250:F1123–1127 (1986).PubMedGoogle Scholar
  23. 23.
    D. Schlondorff, J. Perez, J.A. Satriano, Differential stimulation of PGE2 synthesis in mesangial cells by angiotensin and A23187, Am. J. Phvsiol. 248:C119–C126 (1985).Google Scholar
  24. 24.
    D. Schlondorff, S. DeCandido, J.A. Satriano, Angiotensin stimulates both phospholipase A2 and C in mesangial cells, Am. J. Physiol.. in press.Google Scholar
  25. 25.
    G.A. Zimmerman, T.M. Mclntyre, S.M. Prescott, Thrombin stimulates the adherence of neutrophils to human endothelial cells in vitro, J. Clin. Invest. 76:2235–2246 (1985).PubMedCrossRefGoogle Scholar
  26. 26.
    M.G. Farquhar and G.E. Palade, Functional evidence for the existence of a third cell type in the renal glomerulus, J. Cell Biol. 13:55–87 (1962).PubMedCrossRefGoogle Scholar
  27. 27.
    A.F. Michael, W.F. Keane, L. Raij, R.L. Vernier, S.M. Mauer, The glomerular mesangium, Kidney Int. 17:141–154 (1980).PubMedCrossRefGoogle Scholar
  28. 28.
    L. Baud, J. Hagege, E. Straer, E. Rondeau, J. Perez, R. Ardaillou, Reactive oxygen production by cultured rat glomerular mesangial cells during phagocytosis is associated with stimulation of lipoxygenase activity, J. Exp. Med. 158:1836–1852 (1983).PubMedCrossRefGoogle Scholar
  29. 29.
    L. Baud, J. Perez, R. Ardaillou, Dexamethasone and hydrogen peroxide production by mesangial cells during phagocytosis, Am. J. Phvsiol. 250: F596–F604 (1986).Google Scholar
  30. 30.
    D. Schlondorff, J.A. Satriano, J. Hagege, J. Perez, L. Baud, Effect of platelet-activating factor and serum-treated zymosan on prostaglandin E2 synthesis, arachidonic acid release and contraction of cultured rat mesangial cells, J. Clin. Invest. 73:1227–1231 (1984).PubMedCrossRefGoogle Scholar
  31. 31.
    P.C. Singhal, G.H. Ding, S. DeCandido, N. Franki, R.M. Hays, D. Schlondorff, Endocytosis by cultured mesangial cells and associated changes in prostaglandin E2 synthesis, Am. J. Phvsiol. 252:F627–F634 (1987).Google Scholar
  32. 32.
    R. Neuwirth, P. Singhal, A. Sinha, R.M. Hays, D. Schlondorff, Macromolecular uptake by mesangial cells is enhanced by Fc portion of IgG and is associated with production of PGE2 and platelet-activating factor, in: “Proceedings of the Xth. Int. Congress of Nephrology,” London, (1987).Google Scholar
  33. 33.
    J.R. Sedor, S.W. Carey, S.N. Emancipator, Immune complexes bind to cultured rat glomerular mesangial cells to stimulate superoxide release: evidence for an Fc receptor, J. Immunol. 138:3751–3757, 1987.PubMedGoogle Scholar
  34. 34.
    P. Menè, S.A. Ricanati, G.R. Dubyak, S.N. Emancipator, M.J. Dunn, Stimulation of cytosolic free calcium and contraction by immune complexes in cultured rat mesangial cells, Clin. Res. 35:662A (1987).Google Scholar
  35. 35.
    R. Neuwirth, P. Braquet, D. Schlondorff, Metabolism of [3H] plateletactivating factor by cultured mesangial cells, in: “Proc. of the 2nd Int. on Platelet-activating Factor,” Gatlinburg (1986).Google Scholar
  36. 36.
    N. Ardaillou, J. Hagege, M.-P. Nivez, R. Ardaillou, D. Schlondorff, Vasoconstrictor-evoked prostaglandin synthesis in cultured human mesangial cells, Am. J. Physiol. 248:F240–246 (1985).PubMedGoogle Scholar
  37. 37.
    J. Pfeilschifter, A. Kurtz, C. Bauer, Role of phospholipase C and protein kinase C in vasoconstrictor-induced prostaglandin synthesis in cultured rat renal mesangial cells, Biochem. J. 234:125–130 (1986).PubMedGoogle Scholar
  38. 38.
    J.R. Sedor and H.E. Abboud, Platelet-activating factor stimulates oxygen radical release by cultured rat mesangial cells (abstract), Kidnev Int. 27:222A (1985).Google Scholar
  39. 39.
    R. Neuwirth, P. Singhal, J.A. Satriano, P. Braquet, D. Schlondorff, Effect of platelet-activating factor antagonists on cultured rat mesangial cells, J. Pharm. Exp. Therapeut., in press.Google Scholar
  40. 40.
    J.E. Stork, T.Y. Shen, M.J. Dunn, Stimulation of prostaglandin E2 and thromboxane B2 production in cultured rat mesangial cells by platelet-activating factor: inhibition by a specific receptor antagonist (abstract), Kidney Int. 27:267A (1985).Google Scholar
  41. 41.
    J.V. Bonventre and P.C. Weber, Effect of platelet-activating factor and platelet-derived growth factor on cytosolic free calcium concentration and phospholipase A2 and C activation in glomerular mesangial cells, Kidnev Int. 31:161A (1987).Google Scholar
  42. 42.
    J.J. Berridge and R.F. Irvine, Inositol trisphosphate, a novel second messenger in cellular signal transduction, Nature 312:315–321 (1984).PubMedCrossRefGoogle Scholar
  43. 43.
    M. Kester, P. Menè, G.R. Dubyak, M.J. Dunn, Platelet-activating factor elevates cytosolic free calcium concentration in cultured rat mesangial cells, Clin. Res. 35:550A (1987).Google Scholar
  44. 44.
    A.M. Spiegel, Signal transduction by guanine nucleotide binding proteins, Mol. Cell Endocrinol. 49:1–16 (1987).PubMedCrossRefGoogle Scholar
  45. 45.
    T. Murayama and M. Ui, Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts, J. Biol. Chem. 260:7226–7233 (1985).PubMedGoogle Scholar
  46. 46.
    J. Pfeilschifter and C. Bauer, Pertussis toxin abolished angiotensin II-induced phosphoinositide hydrolysis and prostaglandin synthesis in rat renal mesangial cells, Biochem. J. 236:289–294 (1986).PubMedGoogle Scholar
  47. 47.
    D. Schlondorff, J.A. Satriano, S. DeCandido, Different concentrations of pertussis toxin have opposite effects on agonist-induced PGE2 formation in mesangial cells, Biochem. Biophvs. Res. Comm. 141:39–45 (1986).CrossRefGoogle Scholar
  48. 48.
    R. Barnett, P. Goldwasser, L.A. Scharschmidt, D. Schlondorff, Effects of leukotrienes on isolated rat glomeruli and cultured mesangial cells, Am. J. Phvsiol. 250:F838–844 (1986).Google Scholar
  49. 49.
    L.A. Scharschmidt, M.S. Simonson, M.J. Dunn, Glomerular prostaglandins, angiotensin II, and nonsteroidal antiinflammatory drugs, Am. J. Med. 21:30–42 (1986).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Detlef Schlondorff
    • 1
  1. 1.Albert Einstein College of MedicineNew YorkUSA

Personalised recommendations