Oxygen-dependent injury by a human plasma factor associated with minimal change disease.
The mechanism by which a human plasma factor associated with proteinuria is able to cause experimental glomerular albumin leakage is unknown. This factor (called 100KF) is able to induce glomerular alterations in the rat kidney, similar to those seen in minimal change disease, including loss of glomerular sialoglycoproteins and decreased expression of glomerular ecto-ATPase. It was previously shown that 100KF is able to stimulate release of reactive oxygen species in inflammatory cells in vitro. This prompted us to test whether 100KF-induced injury is oxygen dependent. The expression of glomerular sialoglycoproteins and ecto-ATPase was evaluated by standard histochemistry and computerized image analysis and expressed in arbitrary units. Rat kidney sections were incubated with or without 100KF under normal or oxygen-poor, i.e., nitrogen, conditions, or with supplementation of superoxide dismutase (SOD, 100 U/ml). The effect of 100KF on glomerular ecto-ATPase was oxygen dependent (32.98+/-2.14 under air vs. 65.20+/-5.53 under nitrogen, P< or =0.01), in contrast to the 100KF-induced loss of glomerular sialoglycoproteins that was not significantly altered under nitrogen (62.67+/-10.08 under air vs. 61.74+/-26.05 under nitrogen). Supplementation of SOD to 100KF solution under normal incubation conditions also suggested oxygen-dependent impairment of glomerular ecto-ATPase. Alternate perfusion ex vivo of the rat kidney with 100KF followed by diluted plasma showed that enhanced leakage of plasma proteins could be inhibited with SOD, indicating oxygen dependency of this 100KF-induced enhanced permeability (60.25+/-19.32 microg urinary albumin/ml after 100KF perfusion vs. 25.23+/-12.05 microg/ml after 100KF plus SOD, P< or =0.01). We conclude that the action of 100KF upon specific glomerular matrix molecules is oxygen dependent, as is the albumin leakage induced by 100KF in the present ex vivo model.
Cheung
P K
PK
Department of Pathology, University of Groningen, The Netherlands.
Baller
J F
JF
Bakker
W W
WW
D000251:Adenosine Triphosphatases / Q000096:biosynthesis; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D008970:Molecular Weight; D009402:Nephrosis, Lipoid / Q000097:blood / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000737:chemistry / Q000502:physiology*; D012795:Sialoglycoproteins / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000494:pharmacology
D000418:Albumins; D001798:Blood Proteins; D012795:Sialoglycoproteins; C001643:podocalyxin; D013482:Superoxide Dismutase; D012697:Serine Endopeptidases; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D010100:Oxygen