Tubular catabolism of albumin is associated with the release of an inflammatory lipid.
Proteinuria and tubulointerstitial inflammation (TII) correlate with progression to renal failure in human glomerulonephritis. Various forms of experimental nephrotic syndrome are associated with TII. To study the genesis of TII, we utilized the model of albumin overload. Rats received intraperitoneal bovine serum albumin (BSA) for 1 to 14 days, developing heavy proteinuria. A predominantly macrophage interstitial infiltrate was present at days 3, 7 and 14. The urine of the rats contained a factor chemotactic for macrophages which partitioned into the organic phase with ethyl acetate extraction. TLC and HPLC characteristics were those of a novel, non-polar lipid. Supernatant from the culture of proximal tubule (PT) segments after in vivo or in vitro exposure to high concentrations of lipid-replete BSA showed chemotactic activity with similar chromatographic characteristics. PT cultured with delipidated BSA produced little activity. Thus, the generation of this inflammatory factor occurs as a consequence of tubular metabolism of albumin-borne fatty acids and may contribute to the development of proteinuria-associated TII.
Kees-Folts
D
D
Department of Pediatrics, Hershey Medical Center, Pennsylvania.
Sadow
J L
JL
Schreiner
G F
GF
D000818:Animals; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008264:Macrophages; D009395:Nephritis, Interstitial / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000378:metabolism*
D002630:Chemotactic Factors; D012710:Serum Albumin, Bovine