Eicosanoids and Allograft Rejection

  • M. L. Foegh
  • G. E. Schreiner
  • M. R. Alijani
  • G. B. Helfrich
  • B. S. Khirabadi
  • Peter W. Ramwell
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


The relationship of fatty acids to immunity is of considerable interest (Meade and Mertin, 1978). Their role is now believed to be mediated by their oxidation products, specifically, the eicosanoids. The metabolites of arachidonic acid and drugs that affect their metabolism have far-reaching implications in organ transplantation. One of the major problems in evaluating the role of these eicosanoids is their remarkably diverse effects on many biological systems. The diversity of action appears to be receptor mediated, and receptor classification awaits the synthesis of specific eicosanoid antagonists. Diametrically opposite properties of individual metabolites are apparent in other fields and are well recognized, as is the case with the steroids. Here we are concerned with eicosanoids that are immuno-suppressive and others that clearly promote organ rejection.


Allograft Rejection Cardiac Allograft Allograft Survival Daily Serum Cardiac Allograft Rejection 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Carnuccio, R.M., DiRosa, M., Flower, R.J., and Pinto, A., 1981, The inhibition by hydrocortison of prostaglandin biosynthesis in rat peritoneal leucocytes is correlated with intracellular macrocortin level, Br. J. Pharmacol. 74:322–324.PubMedCrossRefGoogle Scholar
  2. Carrier, R., Cragoe, E.J., Ethier, D., Ford-Hutchinson, A.W., Girard, W., Hall, R.A., Hamel, D., Rokach, J., Share, N.N., Stone, C.A., and Yusko, P., 1984, Studies on L-640,035: A novel antagonist of contractile prostanoids in the lung, Br. J. Pharmacol. 82:389–395.PubMedCrossRefGoogle Scholar
  3. Feuerstein, N., and Ramwell, P.W., 1981, OKY-1581 a potent selective thromboxane synthetase inhibitor, Eur. J. Pharmacol. 69:533–534.PubMedCrossRefGoogle Scholar
  4. Foegh, M.L., Winchester, J.F., Zmudka, M., Helfrich, G.H., Colley, C, Ramwell, P.W., and Schreiner, G.E., 1981, Urine i-TXB2 in renal allograft rejection, Lancet 2:431–434.PubMedCrossRefGoogle Scholar
  5. Foegh, M., Maddox, Y., Winchester, J., Rakowski, T., Schreiner, G., and Ramwell, P.W., 1983, Prostacyclin and thromboxane release from human peritoneal macrophages, Adv. Prostaglandin Thromboxane Leukotriene Res. 12:45–49.Google Scholar
  6. Foegh, M.L., Alijani, M.R., Helfrich, G.H., Khirabadi, B.S., Goldman, M.H., Lower, R.R., and Ramwell, P.W., 1985a, Thromboxane and leutrotrienes in clinical and experimental transplant rejection, Adv. Prostaglandin Thromboxane Leukotriene Res. 13:209–217.Google Scholar
  7. Foegh, M. L., Khirabadi, B., and Ramwell, P. W., 1985b, Prolongation of experimental cardiac allograft survival with thromboxane related drugs, Transplantation (in press).Google Scholar
  8. Ford-Hutchinson, A., Bray, M., Doig, M., Shipley, M, and Smith, M., 1980, Leukotrine B; a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes, Nature 286:264.PubMedCrossRefGoogle Scholar
  9. Gorman, R.R., Wienenga, W., and Miller, O.V., 1979, Independence of the cyclic AMP-lowering activity of thromboxane A2 from platelet release reaction, Biochim. Biophys. Acta 572:95–104.PubMedCrossRefGoogle Scholar
  10. Hirata, F., Schiffman, E., Venkatasubramanian, K., Salomon, D., and Axelrod, J., 1980, A phos-pholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids, Proc. Natl. Acad. Sci. U.SA. 77:2533–2536.CrossRefGoogle Scholar
  11. Hirata, F., Carmine, R., Nelson, C.A., Axelrod, J., Shiffman, E., Warabi, A., Bias, A., Nirenberg, M., Manganiello, V., Vaughan, M., Kumagai, S., Green, I., Decker, J., and Steinberg, A., 1981, Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic disease, Proc. Natl. Acad. Sci. U.S.A. 78:3190–3194.PubMedCrossRefGoogle Scholar
  12. Jaffe, B.M., Moore, T.C, and Vigran, T.S., 1975, Tissue levels of prostaglandin E following heterotopic rat heart allografting, Surgery 78:481–484.PubMedGoogle Scholar
  13. Jamieson, S. W., Burton, N., and Reitz, B., 1979, Platelets, sulfinpyrazone and organ graft rejection, in: Cardiovascular Actions of Sulfinpyrazon: Basic and Clinical Research (M. McCregor, J. Mustard, M. Oliver, and S. Sherry, eds.), Symposia Specialist, Miami, pp. 229–243.Google Scholar
  14. Kawahara, Y., Yamarishi, J., Furuta, Y., Kaibuchi, K., Takai, Y., and Fukuzahi, H., 1983, Elevation of cytoplasmic free calcium concentration by stable thromboxane A2 analogue in human platelets, Biochem. Biophys. Res. Commun. 117:663–669.PubMedCrossRefGoogle Scholar
  15. Kelly, J.P., Johnson, M.C, and Parker, C.W., 1979, Effect of inhibition of arachidonic acid metabolism on mitogenesis in human lymphocytes: Possible role of thromboxanes and products of the lipoxygenase pathway, J. Immunol. 122:1563–1571.PubMedGoogle Scholar
  16. Kort, W.J., Bonta, I.L., Adolfs, M.J.P., and Westbroek, D.L., 1982, Synergism of (15 5-15-methylprostaglandin E1 with either azathioprine or prednisolone on the survival of heart allografts in rats, Prostaglandins Leukotrienes Med. 8:661–664.Google Scholar
  17. Leithner, C, Sinzinger, H., and Schwarz, M., 1981, Treatment of chronic kidney transplant rejection with prostacyclin—reduction of platelet deposition in the transplant; prolongation of platelet survival and improvement of transplant function, Prostaglandins 22:783–788.PubMedCrossRefGoogle Scholar
  18. Leithner, C.G., Sinzinger, H., Schwartz, M., Pohanka, E., and Syre, G.H., 1983, Increased deposition of indium-111 labelled platelets in chronically rejected kidney transplants, Clin. Nephrol. 18:311–313.Google Scholar
  19. Leung, K.H., and Minich, E., 1980, Prostaglandin modulation of development of cell-mediated immunity in culture, Nature 288:597–600.PubMedCrossRefGoogle Scholar
  20. Maddox, Y., Shapiro, R., Goldman, M., Lower, R., and Ramwell, P., 1984, Contractile effects of leukotriene C4 and the thromboxane mimic U46619 on human pulmonary arteries and veins in vitro, in: Clinically Related Lipids, Vol. 2 (T. J. Powles, R. S. Bochman, K. V. Honn, and P. Ramwell, eds.), Alan R. Liss, New York, pp. 47–65.Google Scholar
  21. Maddox, Y., Cunard, C, Shapiro, R. Mitchell, G., Lower, R., and Ramwell, P., 1985, A comparison of the contractile responses of rodent and human pulmonary vascular segments to icosanoids, in this volume.Google Scholar
  22. Mead, C.J., and Mertin, J., 1978, Fatty acids and immunity, Adv. Lipid Res. 16:127–65.Google Scholar
  23. Mertin, J., and Hunt, R., 1976, Influence of polyunsaturated fatty acids on survival of skin allografts and tumor incidence in mice, Proc. Nat. Acad. Sci. 3:928–931.CrossRefGoogle Scholar
  24. Naccache, P.H., Sha’afi, R.I., Borgeat, P., Goetzl, E.J., 1981, Mono-and dihydroxy eicosatetraenoic acids alter calcium homeostasis in rabbit neutrophils, J. Clin. Invest. 67:1584–1588.PubMedCrossRefGoogle Scholar
  25. Oluwole, S., Wang, T., Fawwaz, R., Sataki, K., Nowygrod, R., Reemtsme, K., and Hardy, M.A., 1981, Use of Indium-III-labelled cells in measurement, of cellular dynamics of experimental cardiac allograft rejection, Transplant 31:51–55.CrossRefGoogle Scholar
  26. Payan, O.G., and Goetzl, E., 1983, Specific suppression of human T-lymphocyte function by leukotriene B4, J. Immunol. 131:551–553.PubMedGoogle Scholar
  27. Quagliata, F., Lawrence, V.J.W., and Phillips-Quagliata, J.M., 1973, Prostaglandin E1 as a regulator of lymphocyte function, Cell Immunol. 6:457–65.PubMedCrossRefGoogle Scholar
  28. Rola-Pleszczynski, M., Borgeat, P., and Sirois, P., 1983, Leukotriene B4 induces human suppressive lymphocytes, Biochem. Biophys. Res. Commun. 108:1531–1537.CrossRefGoogle Scholar
  29. Shaw, J.F.L., 1983, Prolongation of rat cardiac allograft survival by treatment with prostacyclin or aspirin during acute rejection, Transplant 5:526–529.CrossRefGoogle Scholar
  30. Shaw, J. F. L., 1984, Drugs affecting the prostaglandin synthetic pathway and rat heart allograft survival, in: Platelets, Prostaglandins and Cardiovascular System, Abstract, Florence, p. 130.Google Scholar
  31. Sinzinger, H., Leithner, C, and Schwarz, M., 1981, Monitoring of human kidney transplants using quantification of autologous 111 indium-oxine platelet label deposition–beneficial effect of PGI2-treatment in acute (AR) and chronic (CR) rejection, Thomb. Haemostas. 46:263.Google Scholar
  32. Smith, N., Chandler, S., Hawker, R.J., Hawke, L.M., and Barnes, A.D., 1979, Indium labelled autologous platelets as diagnostic aid after renal transplantation, Lancet 1:1241–1242.CrossRefGoogle Scholar
  33. Strom, T.B., and Carpenter, C.B., 1983, Prostaglandin as an effective antirejection therapy in rat renal allograft recipients, Transplant 35:279–281.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • M. L. Foegh
    • 1
  • G. E. Schreiner
    • 1
  • M. R. Alijani
    • 2
  • G. B. Helfrich
    • 2
  • B. S. Khirabadi
    • 2
  • Peter W. Ramwell
    • 2
  1. 1.Department of Medicine, Division of NephrologyGeorgetown University Medical CenterUSA
  2. 2.Department of Surgery, Division of TransplantationGeorgetown University Medical CenterUSA

Personalised recommendations