Reactivity of mesangial cells with aberrantly glycosylated IgA: modulation by angiotensin-converting enzyme inhibitors

The aim of the present study was to evaluate the modulating effect of angiotensin-converting enzyme inhibitors (ACE-I) on the reactivity of mesangial cells (MC) challenged with aberrantly glycosylated IgA. In vitro prepared desialylated and degalactosylated IgA (deSia/deGal IgA) were incubated with cultured MC in the presence or absence of enalapril 10-100 ng/mL. DeSia/deGal IgA significantly depressed the MC proliferation rate, simultaneously enhancing the apoptotic rate. A negative control on vascular endothelial growth factor synthesis was found which was mediated by enhanced inducible macrophage-type nitric oxide synthase activity. The coincubation with enalapril 100 ng/mL significantly reversed these effects. Aberrantly glycosylated IgA induced clear expression of alpha-smooth muscle cell actin in MC, suggesting an acquisition of miofibroblast-like phenotype. The ACE-I, again, significantly inhibited this effect. In order to evaluate the intracellular mechanisms activated by ACE-I, the authors aimed to investigate the modulating activity of aberrantly glycosylated IgA and ACE-I on the nuclear factor (NF)-kappaB transcriptional factor system. In MC treated with aberrantly glycosylated IgA, the activation of the NF-kappaB/IkappaB complex leading to translocation of NF-kappaB into the nucleus, was detected. The phenomenon was significantly blunted by the co-incubation with ACE-I. The present study indicates that ACE-I may limit the effects on MC of the altered glycosylation of circulating IgA molecules in patients with IgA nephropathy via the inhibition of the transcriptional factor NF-kappaB. These in vitro results might add further support to the possible benefit of ACE-I therapy in progressive IgA nephropathy.