Pathogenesis of IgA nephropathy: in vitro activation of human mesangial cells by IgA immune complex leads to cytokine secretion.
IgA immune complex (IC) plays a crucial role in the pathogenesis of IgA nephropathy (IgAN). As IgA-IC is not itself cytotoxic, other mediators may be involved in the pathogenesis. In order to elucidate the mechanisms by which IgA-IC mediates renal injury in IgAN, the ability of IgA-IC to 'activate' cultured human mesangial cells (HMC) was studied. HMC were incubated with nephritogenic IgA-IC, containing a MOPC-315 plasmacytoma-derived IgA anti-dinitrophenyl (DNP) and DNP-conjugated bovine serum albumin. The cells showed morphological changes, an accelerated rate of proliferation, and increased production of interleukin-1 (IL-1), interleukin-6 (IL-6), platelet activating factor (PAF) and generation of superoxide anion. The enhancement of IL-1 and IL-6 mRNA expression in HMC incubated with IgA-IC was identified by dot blot analysis. Northern blot hybridization also demonstrated an augmented IL-6 mRNA expression in HMC treated with IgA-IC. These results suggest that nephritogenic IgA-IC may amplify the proliferation of HMC and the production of immune/chemical mediators and superoxide anion thereby resulting in the renal lesions of IgAN.
Chen
A
A
Department of Medical Research, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Chen
W P
WP
Sheu
L F
LF
Lin
C Y
CY
D000293:Adolescent; D000328:Adult; D000936:Antigen-Antibody Complex / Q000276:immunology*; D015152:Blotting, Northern; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D005920:Glomerular Mesangium / Q000166:cytology / Q000276:immunology*; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis*; D010972:Platelet Activating Factor / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D013481:Superoxides / Q000378:metabolism
D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D013481:Superoxides