Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy.
Individual animals in the closed colony population of ddY mice were analyzed to clarify the major cause of age-dependent elevation of serum IgA and the appearance of human IgA nephropathy (IgAN)-like symptoms. Based on the serum IgA levels, the mice were classified into two subgroups. One was a high serum IgA group with some manifestations of IgAN through aging (ddY(High)), and the other was a normal serum IgA group without IgAN (ddY(Norm)). The ratio of urinary IgA to serum IgA was significantly reduced in ddY(High) mice, suggesting an impaired IgA clearance via secretion through the epithelial barrier. The actual clearance rate of the intravenously injected dimeric IgA in ddY(High) mice was found to be slower than that in ddY(Norm) mice. Furthermore, we found that the polymeric Ig receptors (pIgRs) that mediate transcytosis of IgA were poorly expressed in the glomeruli as well as in the intestine of ddY(High) mice, whereas the pIgRs were more abundantly expressed in ddY(Norm) mice. In addition, the comparative study using polymerase chain reaction showed that decreased pIgR expression occurred at the transcriptional level in the ddY(High) population. Taken together, these results suggest that a systemic defect in pIgR expression may result in impaired IgA secretion and accumulation of IgA in the serum of ddY(High) mice. The age-dependent changes of pIgR expression in the dimeric IgA secretion sites of ddY(High) mice suggest a possible cause for the elevation of serum IgA level and the pathogenesis of IgAN-like disease.
Yanagihara
Takeshi
T
Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
Kumagai
Yoshihiro
Y
Norose
Yoshihiko
Y
Moro
Itaru
I
Nanno
Masanobu
M
Murakami
Mutsumi
M
Takahashi
Hidemi
H
D000375:Aging / Q000502:physiology*; D000818:Animals; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
D007070:Immunoglobulin A; D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin