Glomerular leukotriene synthesis in Heymann nephritis

Abstract

The glomerular synthesis of LTB4 was assessed in glomeruli isolated from rats with passive Heymann nephritis (PHN). PHN was induced by a single intravenous administration of proteinuric doses of immune sera raised in sheep against rat brush border tubular fraction Fx1A. At various time points following induction of the disease glomeruli were isolated and LTB4 synthesis was assessed under basal and phospholipase A2 activation conditions. LTB4 was measured by high pressure liquid chromatography and radioimmunoassay and was identified by UV spectroscopy. The role of complement system in mediating glomerular LTB4 synthesis was also assessed in a group of decomplemented rats using cobra venom factor and at various time points following administration of immune serum. Following induction of PHN, enhanced glomerular LTB4 synthesis was observed as early as one hour, peaked at five hours and returned toward control levels over the subsequent four days. The peak in glomerular LTB4 synthesis did not correlate with changes in glomerular neutrophiles or macrophages. A second increment of LTB4 synthesis occurred at the onset of heavy proteinuria (day 5). Complement depletion reduced proteinuria and the enhancement in LTB4 synthesis at day 5 but had no effect at earlier time points. The observations indicate that in non-inflammatory forms of glomerular immune injury the glomerular arachidonate 5-lipoxygenation is enhanced. This phenomenon has no apparent relationship with increased glomerular permeability to protein and may reflect the presence or activation of a leukotriene producing cell following intraglomerular interactions of Fx1A antigen, anti-Fx1A antibody and complement.