BINDING OF DIMERIC AND POLYMERIC IGA TO RAT RENAL MESANGIAL CELLS ENHANCES THE RELEASE OF INTERLEUKIN-6

Binding of dimeric and polymeric IgA to rat renal mesangial cells enha nces the release of interleukin 6. The mesangium plays a crucial role in processes of inflammation in the kidney. Since deposits of IgA in t he mesangium in patients with IgA nephropathy suggest a role for IgA i n the inflammatory process, we investigated whether IgA is able to bin d to cultured rat mesangial cells (MC) in vitro and induce activation of MC. As a source of IgA, monomeric (mIgA), dimeric (dIgA) and polyme ric IgA-alpha-DNP (pIgA) rat monoclonal antibodies were used. FACS ana lysis indicated binding of dIgA and pIgA to MC while only a small perc entage of the cells exhibited binding of mIgA. Additional experiments employing radiolabeled IgA revealed a time- and dose-dependent binding of I-125-dIgA and I-125-pIgA with 6.10(6) binding sites for dIgA with an affinity of 5.5.10(6) M(-1) and 7.2.10(6) binding sotes/cell for p IgA with an affinity of 1.2.10(6) M(-1). As compared to I-125-dIgA and I-125-pIgA, little binding of I-125-mIgA to MC occurred; the binding of dIgA and pIgA was not influenced by excess cold BSA, IgG or asialof etuin. Since some studies have suggested that fibronectin might intera ct with IgA, the binding of IgA to MC in the presence or absence of fi bronectin or the RGD fragment was also analyzed. However no influence of fibronectin or the RGD fragment on binding of dIgA and pIgA to MC w as observed. As a measure for activation of MC by IgA, the production of IL-6 by MC was analyzed. Dimeric IgA and pIgA both induced a dose-d ependent increase of IL-6 production by MC. These studies suggest that especially dIgA and pIgA are potent activators of MC, while mIgA is r elatively ineffective in this respect.