Abstract
Thromboxane, excreted in the urine in increased amounts in glomerular, vascular and tubulo-interstitial diseases, is considered to originate from the kidney. The localization of thromboxane synthase, a key enzyme of arachidonic acid metabolism, was studied in the human kidney by immunohistology using the monoclonal antibody Tü 300. In the interstitial tissue dendritic reticulum cells surrounding the tubules expressed high concentrations of the enzyme. In glomeruli the enzyme was weakly expressed in podocytes. This was confirmed by co-localization with an antiserum directed to podocalyxin, a marker of the visceral epithelial cells. In the study of various kidney diseases, massive accumulation of thromboxane synthase containing cells was observed in interstitial diseases, whereas in glomerular diseases there were no differences from normal kidney; in a case of thrombotic microangiopathy podocytes exhibited an increase in thromboxane-synthase. The thromboxane-synthase positive infiltrating interstitial cells were shown by conventional light microscopy to be mononuclear phagocytic cells. The physiological sources of renal thromboxane are dendritic reticular cells and podocytes. In interstitial renal disease infiltrating cells of the monocyte/macrophage system constitute the major site of thromboxane synthesis. In glomerular disease, a characteristic alteration of thromboxane-synthase was not found.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ardaillou N, Nivez MP, Striker G, Ardaillou R (1983) Prostaglandin synthesis by human glomerular cells in culture. Prostaglandins 26:773–784
Benigni A, Chiabrando C, Perico N, Fabekku R, Patrono C, Fitzgerald GA, Remuzzi G (1989) Renal metabolism and urinary excretion of thromboxane B2 in the rat. Am Physiol Soc F77–F85
Brass LF, Shaller CC, Belmonte EJ (1987) Inositol 1,4,5-triphosphate-induced granule secretion in platelets. J Clin Invest 79:1269–1275
Chatziantoniou C, Papanikolaou N (1989) The role of prostaglandin and thromboxane synthesis by the glomeruli in the development of acute renal failure. Eicosanoids 2:157–161
Coffman TM, Yarger WE, Klotman PE (1985) Functional role of thromboxane production by acutely rejecting renal allografts in rats. J Clin Invest 75:1242–1248
Coffman TM, Ruiz P, Sanfilippo F, Klotman PE (1989) Chronic thromboxane inhibition preserves function of rejecting rat renal allografts. Kidney Int 35:24–30
DeWitt DL, Smith WL (1983) Purification of prostacyclin synthase from bovine aorta by immunoaffinity chromatography. J Biol Chem 258:3285–3293
Floege J, Topley N, Wessel K, Kaever V, Radeke H, Hoppe J, Kishimoto T, Resch K (1990) Monokines and platelet-derived growth factor modulate prostanoid production in growth arrested, human mesangial cells. Kidney Int 37:859–869
Foegh ML, Zmudka M, Cooley C, Winchester JF, Helfrich GB, Ramwell GW, Schreiner GE (1981) Urine immunoreactive thromboxane B2 in renal allograft rejection. Lancet II:431–434
Folkert VW, Schlöndorff D (1979) Prostaglandin synthesis in isolated glomeruli. Prostaglandins 17:79–86
Frohlich JC, Wilson TW, Sweetman BJ, Smigel M, Nies AS, Carr K, Watson JT, Oates JA (1975) Urinary prostaglandins: identification and origin. J Clin Invest 55:763–770
Hamberg M, Svensson J, Samuelsson B (1975) Thromboxanes. A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 72:2994
Hassid A, Konieczkowski M, Dunn MJ (1979) Prostaglandin synthesis in isolated rat kidney glomeruli. Proc Natl Acad Sci USA 76:1155–1159
Haurand M, Ullrich V (1985) Isolation and characterization of thromboxane synthase from human platelets as a cytochrome P-450 enzyme. J Biol Chem 260:150–159
Hopkins UK, Sun FF, Gorman RR (1978) Thromboxane A2 in human lung fibroblasts WI-38. Biochem Biophys Res Commun 85:827
Kerjaschki D, Poczewski H, Dekan G, Horvat R, Balzar E, Kraft N, Atkins RC: (1986) Identification of a major sialoprotein in the glycocalyx of human visceral glomerular epithelial cells. J Clin Invest 78:1142–1149
Kreisberg JI, Kurnovsky MJ, Levine L (1982) Prostaglandin production by homogeneous cultures of rat glomerular epithelial and mesangial cells. Kidney Int 22:355–359
Kreisberg JI, Venkatachalam M, Troyer D (1985) Contractile properties of cultured glomerular mesangial cells. Am J Physiol 249: F457-F463
Lelcuk S, Alexander F, Kolzik L, Valeri CR, Shepro D, Hechtman HB (1985) Prostacyclin and thromboxane A2 moderate postischemic renal failure. Surgery 98:207–212
Lianos EA, Andres Ga, Dunn MJ (1983) Glomerular prostaglandin and thromboxane synthesis in rat nephrotoxic serum nephritis. J Clin Invest 72:1439–1448
Mangino MJ, Brunt EM, Von Doersten P, Anderson CB (1989) Effects of the selective thromboxane synthesis inhibitor CGS-12970 on experimental acute renal allograft rejection. J Pharmacol Exp Ther 248:23–28
Mason DY (1988) Immunocytochemical labeling of monoclonal antibodies by the APAAP immunoalkaline phosphatase technique. In: Bullock GR, Petrusz P (eds) Techniques in immunocytochemistry. Academic Press, San Diego, pp. 35–42
Mené P, Dunn MJ (1986) Contractile effects of TxA2 and endoperoxide analogues on cultured rat glomerular mesangial cells. Am J Physiol 251: F1029-F1035
Mené P, Dunn MJ (1988) Eicosanoids and control of mesangial cell contraction. Circ Res 62:916–925
Mené P, Dubyak GR, Abboud HE, Dunn MJ (1988) Phospholipase C activation by prostaglandins and thromboxane A2 in cultured mesangial cells. Am J Physiol 255: F1059-F1069
Mené P, Abbound H, Dunn MJ (1990) Regulation of human mesangial cell growth in culture by thromboxane A2 and prostacyclin. Kidney Int 38:232–239
Morrison AR, Nishikawa K, Needleman P (1977) Unmasking of thromboxane A2 synthesis by ureter obstruction in the rabbit kidney. Nature 269:259–260
Murota S, Kawamura M, Morita I (1978) Transformation of arachidonic acid into thromboxane B2 by the homogenates of activated macrophages. Biochim Biophys Acta 528:507
Needleman P, Moncada S, Bunting S, Vane JR, Hamberg M, Samuelsson B (1976) Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides. Nature 261:558
Needleman P, Kulkarni PS, Raz A (1977) Coronary tone modulation. Formation and actions of prostaglandins, endoperoxides and thromboxanes. Science 195:406
Nüsing R, Schneider-Voss S, Ullrich V (1990a) Immunoaffinity purification of human thromboxane synthase. Arch Biochem Biophys 280:325–330
Nüsing R, Wernet MP, Ullrich V (1990b) Production and characterization of polyclonal and monoclonal antibodies against human thromboxane synthase. Blood 76:80–85
Nüsing R, Lesch R, Ullrich V (1990c) Immunhistochemical localization of thromboxane synthase in human tissues. Eicosanoids 3:53–58
Nüsing R, Sauter G, Fehr P, Dürmüller U, Kasper M, Gudat F, Ullrich V (1992) Localization of thromboxane synthase in human tissues by monoclonal antibody Tü 300. Virchow Arch [A] 421:249–254
Patrono C, Ciabattoni G, Remuzzi G, Gotti E, Bombardieri S, Di Munno O, Tartarelli G, Cinotti GA, Simonetti BM, Pierucci A (1985) Functional significance of renal prostacyclin and thromboxane A2 in patients with systemic lupus erythematosus. J Clin Invest 76:1011–1018
Petrulis AS, Aikawa M, Dunn M (1981) Prostaglandin and thromboxane synthesis by rat glomerular epithelial cells. Kidney Int 20:469–474
Pierucci A, Simonetti BM, Pecci G, Mavrikakis G, Feriozzi S, Cinotti GA, Patrignani P, Ciabattoni G, Patrono C (1989) Improvement of renal function with selective thromboxane antagonism in lupus nepritis. N Engl J Med 320:421–425
Purkerson M, Joist JH, Yates J, Valdes A, Morrison A, Klahr S (1985) Inhibiton of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation. Proc Natl Acad Sci USA 82:193–197
Remuzzi G, Imberti L, Rossini M, Morelli C, Carminati C, Catteneo GM, Bertani T (1984) Increased glomerular thromboxane synthesis as a possible cause of proteinuria in experimental nephrosis. J Clin Invest 75:94–101
Roberts LJ, Sweetman BJ, Oates JA (1981) Metabolism of thromboxane B2 in man. J Biol Chem 256:8384–8391
Saito H, Ideura T, Takeuchi JI (1984) Effects of a selective thromboxane A2 synthetase inhibitor on immune complex glomerulonephritis. Nephron 36:38–45
Schlöndorff (1987) The glomerular mesangial cell: an expanding role for a specialized pericyte. FASEB J. 1:272–281
Schwartz D, DeSchryver-Kecskemeti K, Needleman P (1984) Renal arachidonic acid metabolism and cellular changes in the rabbit renal vein constricted kidney: inflammation as a common process in renal injury models. Prostaglandins 27:605–613
Shibouta Y, Terashita Z, Inada Y, Nishikawa K, Kikuchi S (1981) Enhanced thromboxane A2 biosynthesis in the kidney of spontaneously hypertensive rats during development of hypertension. Eur J Pharmacol 70:247–256
Shibouta Y, Terashita Z, Inada Y, Nishikawa K (1985) Delay of the initiation of hypertension in spontaneously hypertensive rats by CV-4151, a specific thromboxane A2 synthetase inhibitor. Eur J Pharmacol 109:135–144
Sraer J, Foidart J, Chansel D, Mahieu P, Kouznetzova B, Ardaillou R (1979) Prostaglandin synthesis by mesangial cells and epithelial glomerular cultured cells. FEBS Lett 104
Sraer J, Sraer JD, Chansel D, Russo-Marie F, Kouznetzova B, Ardaillou R (1989) Prostaglandin synthesis by isolated rat renal glomeruli. Mol Cell Endocrinol 16:29–37
Ullrich V, Graf H (1984) Prostacyclin and thromboxane synthase as P-450 enzymes. Trends Pharmacol Sci 5:352
Zoja C, Benigni A, Livio M, Bergamelli A, Orisio S, Abbate M, Bertani T, Remuzzi G (1989) Selective inhibition of platelet thromboxane generation with low-dose aspirin does not protect rats with reduced renal mass from the development of progressive disease. Am J Pathol 5:1027–1039
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nüsing, R., Ullrich, V., Fehr, P.M. et al. The localization of thromboxane synthase in normal and pathological human kidney tissue using a monoclonal antibody Tü 300. Vichows Archiv A Pathol Anat 424, 69–74 (1994). https://doi.org/10.1007/BF00197395
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00197395