Metabolism of properdin in normal subjects and patients with renal disease.
Properdin deposition has been recognized in glomeruli of patients with acute and chronic nephritis and lupus nephritis, and low serum properdin levels have been found in these disorders. These findings suggest that properdin may be involved in the production of glomerular damage and that low properdin levels may be due to hypercatabolism. The study was designed to examine the metabolism of properdin in normal subjects and to look for an abnormality in five patients with systemic lupus erythematosus with renal involvement and in six patients with membranoproliferative glomerulonephritis or dense deposit disease (MPGN). Highly purified human properdin was prepared by elution from zymosan, followed by DEAE-cellulose and carboxymethyl-Sephadex chromatography, and labeled with 125I by the iodine monochloride method. Parameters of metabolism were determined by monitoring plasma and urinary radioactivity at frequent intervals after the intravenous injection of 1-2 muCi of labeled material. The fractional catabolic rate (FCR) of properdin in normal subjects was found to have a very narrow range of 0.78-1.0,% of the plasma pool per hour (mean 0.95%). In systemic lupus erythematosus, the FCR was regularly elevated with a range of 1.21-2.30% (mean 1.70%). In MPGN, FCR was elevated in three patients (1.22, 1.94, and 2.08%) and within or below the normal range in three (0.78, 1.00, and 1.00%). Properdin levels were reduced in two patients who had the highest FCR's noted in the study. Properdin synthetic rates in normals varied from 4.1 to 14.3 mug/kg per h (mean 9.1) and was not found to be reduced in any patient. Properdin catabolism was found to be normal in a patient deficient in the C3b inactivator. These studies show that properdin is hypercatabolized in patients with renal disease and that decreased properdin levels when they occur in these patients can be entirely explained on the basis of this hypercatabolism.
D000293:Adolescent; D000328:Adult; D002648:Child; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003182:Complement C5 / Q000032:analysis; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009393:Nephritis / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D011414:Properdin / Q000378:metabolism*
D003176:Complement C3; D003181:Complement C4; D003182:Complement C5; D011414:Properdin