Neutrophils in IgA nephropathy

Neutrophil participation is prominent in proliferative forms of glomerulonephritis. They are recruited by antibody-mediated chemoattractant complement fragments. Monocyte and endothelial derived cytokines or adhesion molecules may also recruit these cells. In most situations of inflammation, neutrophils induce injury by the release of reactive oxygen radicals and their production of lysosomal proteolytic enzymes. The clinical importance of neutrophils in mediating glomerular injury in IgA nephropathy (IgAN) has often been downplayed, although it has been recognized that IgA is involved in the initiation of intracellular oxidative metabolism in normal neutrophils. That disordered neutrophil activation could be relevant to the pathogenesis of IgAN seems likely from their prominent infiltration in glomerular capillaries in the acute phase of primary IgAN, increased expression of complement 3 receptors on neutrophils from patients with IgAN, and increased oxidative metabolism of neutrophils in these patients. Furthermore, recent data revealed heat aggregated forms of IgA prepared from patients with IgAN exert an up-regulatory effect on calcium mobilization, inositol triphosphate production, and oxidative metabolism in human neutrophils. Interestingly, the plasma level of E-selectin, mainly derived from activated vascular endothelial cells upon interaction with neutrophil, was elevated following synpharyngitic macrohaematuria in patients with IgAN. There was also a significant stepwise increase in circulating E-selectin associated with increased histopathologic severity in these patients. These data tend to support the notion that neutrophils could be activated in IgAN despite lack of acute clinical exacerbation and may potentially be participating in the inflammatory process of glomerular and interstitial injury.