Leukotriene D4 is a mediator of proteinuria and glomerular hemodynamic abnormalities in passive heymann nephritis

Tetsuo Katoh, Elias A. Lianos, Megumu Fukunaga, Kihito Takahashi, Kamal F. Badr

Research output: Contribution to journalArticle

Abstract

We assessed the role of leukotrienes (LTs) in Munich-Wistar rats with passive Heymann nephritis (PHN), an animal model of human membranous nephropathy. 10 d after injection of anti-Fx1A antibody, urinary protein excretion rate (Upr) in PHN was significantly higher than that of control. Micropuncture studies demonstrated reduced single nephron plasma flow and glomerular filtration rates, increased transcapillary hydrualic pressure difference, pre- and postglomerular resistances, and decreased ultrafiltration coefficient in PHN rats. Glomerular LTB4 generation from PHN rats was increased. Administration of the 5-LO activating protein inhibitor MK886 for 10d markedly blunted proteinuria and normalized glomerular hemodynamic abnormalities in PHN rats. An LTD4 receptor antagonist SK&F 104353 led to an immediate reduction in Upr and to reversal of glomerular hemodynamic impairment. Ia( + ) cells/glomerulus were increased in PHN rats. In x-irradiated PHN rats, which developed glomerular macrophage depletion, augmented glomerular LT synthesis was abolished. Thus, in the autologous phase of PHN, LTD4 mediates glomerular hemodynamic abnormalities and a hemodynamic component of the accompanying proteinuria. The synthesis of LTD4 likely occurs directly from macrophages or from macrophage-derived LTA4, through LTC4 synthase in glomerular cells.

Original languageEnglish (US)
Pages (from-to)1507-1515
Number of pages9
JournalJournal of Clinical Investigation
Volume91
Issue number4
StatePublished - Apr 1993
Externally publishedYes

Keywords

  • Glomerular pressure
  • Leukotriene D4
  • Lipoxygenase
  • Passive Heymann nephritis
  • Proteinuria

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Katoh, T., Lianos, E. A., Fukunaga, M., Takahashi, K., & Badr, K. F. (1993). Leukotriene D4 is a mediator of proteinuria and glomerular hemodynamic abnormalities in passive heymann nephritis. Journal of Clinical Investigation, 91(4), 1507-1515.