Rapid deposition of glomerular IgA in BALB/c mice by nivalenol and its modifying effect on high IgA strain (HIGA) mice.
To clarify the underlying mechanisms of IgA nephropathy (IgAN) induced by nivalenol (NIV), a trichothecene mycotoxin, we examined the time and dose relationships of glomerular deposition of IgA by NIV in BALB/c mice (Experiment 1), and also evaluated the modification of NIV on spontaneous IgAN in an inbred murine model, a high IgA strain (HIGA), during its early stage of pathogenesis (Experiment 2). In Experiment 1, female BALB/c mice were given a diet containing 0, 12, or 24 ppm concentration of NIV for 4 or 8 weeks. An increase in serum IgA levels was found at 24 ppm from 4 weeks. At week 8 of treatment, dose-dependent increases in serum IgA levels and glomerular deposition of IgA and IgG were observed without accompanying histopathological glomerular changes. On the other hand, in Experiment 2, control HIGA mice exhibited rather high levels of serum IgA as compared with BALB/c mice from 4 weeks of experiment as well as glomerular deposition of IgA and IgG and mesangial proliferation as revealed at week 8. NIV at 24ppm further increased serum IgA in this strain; however, it did not enhance glomerular immunoglobulin deposition or histopathological lesion. These results suggest that NIV-induced increase of serum IgA levels may be primarily responsible for glomerular immunoglobulin deposition; however, NIV does not enhance glomerular IgA deposition that may lead to exacerbation of predisposed IgAN in the short term, irrespective of the further elevation of serum IgA from the high basal levels.
Dewa
Yasuaki
Y
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Kemmochi
Sayaka
S
Kawai
Masaomi
M
Saegusa
Yukie
Y
Harada
Tomoaki
T
Shimamoto
Keisuke
K
Mitsumori
Kunitoshi
K
Kumagai
Susumu
S
Sugita-Konishi
Yoshiko
Y
Shibutani
Makoto
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology*; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D014255:Trichothecenes / Q000633:toxicity*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014255:Trichothecenes; C038405:nivalenol; C007262:deoxynivalenol