Binding of dimeric and polymeric IgA to rat renal mesangial cells enhances the release of interleukin 6.
The mesangium plays a crucial role in processes of inflammation in the kidney. Since deposits of IgA in the mesangium in patients with IgA nephropathy suggest a role for IgA in the inflammatory process, we investigated whether IgA is able to bind to cultured rat mesangial cells (MC) in vitro and induce activation of MC. As a source of IgA, monomeric (mIgA), dimeric (dIgA) and polymeric IgA-alpha-DNP (pIgA) rat monoclonal antibodies were used. FACS analysis indicated binding of dIgA and pIgA to MC while only a small percentage of the cells exhibited binding of mIgA. Additional experiments employing radiolabeled IgA revealed a time- and dose-dependent binding of 125I-dIgA and 125I-pIgA with 6 x 10(6) binding sites for dIgA with an affinity of 5.5 x 10(6) M-1 and 7.2 X 10(6) binding sites/cell for pIgA with an affinity of 1.2 x 10(6) M-1. As compared to 125I-dIgA and 125I-pIgA, little binding of 125I-mIgA to MC occurred; the binding of dIgA and pIgA was not influenced by excess cold BSA, IgG or asialofetuin. Since some studies have suggested that fibronectin might interact with IgA, the binding of IgA to MC in the presence or absence of fibronectin or the RGD fragment was also analyzed. However no influence of fibronectin or the RGD fragment on binding of dIgA and pIgA to MC was 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-dependent increase of IL-6 production by MC.(ABSTRACT TRUNCATED AT 250 WORDS)
van den Dobbelsteen
M E
ME
Department of Nephrology, University Hospital Leiden, The Netherlands.
van der Woude
F J
FJ
Schroeijers
W E
WE
van den Wall Bake
A W
AW
van Es
L A
LA
Daha
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D001704:Biopolymers / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D007070:Immunoglobulin A / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001704:Biopolymers; C045281:IgA receptor; D007070:Immunoglobulin A; D015850:Interleukin-6; D011961:Receptors, Fc; C034639:polymeric IgA