Role of neutrophil elastase in the development of renal necrotizing vasculitis

To assess the pathogenetic mechanisms of renal vasculitis, we performed immunohistochemical studies using renal biopsy specimens which were obtained from a patient with microscopic polyangiitis during both the acute and the convalescent phase. Intense infiltration and aggregation of neutrophil elastase positive (NE+) cells were observed especially in the periglomerular and perivascular areas in the first biopsy in which vascular necrosis, rupture of Bowman's capsule, and necrotizing glomerulonephritis were present. In addition to intracellular NE expression, NE was also expressed extracellularly in both segmental glomerular tufts and the interstitium. Intensity of NE immunoreactivity in the glomeruli was closely correlated with the development of glomerular necrotizing lesions and crescents, but no such correlation was detected with the infiltration of macrophages, T cells or B cells. In the second biopsy (convalescent phase), patchy intracellular NE expression was present in the interstitium, but no aggregation of NE+ cells or extracellular NE expression was detected in either the glomeruli or the interstitium. These findings suggest that recruitment of polymorphonuclear leukocytes in perivascular and periglomerular areas as well as in glomerular tufts, and subsequent extracellular release of NE in situ may play an important role in the development of renal vasculitis characterized by vascular necrosis, rupture of Bowman's capsule, and tuft necrosis.