Evaluation of the proteolytic activity of factor D accumulated as an active serine protease in patients with chronic renal failure.
Complement factor D, a complement system serine protease, circulating in vivo as its active form, accumulates in patients with chronic renal failure. The pathophysiological role of this active protease in these patients was examined by studies on activities of excess factor D on 10 synthetic peptide substrates for some usual serine proteases. The most sensitive of these substrates to factor D was Boc-Gln-Ala-Arg-MCA, which is used as a substrate for trypsin. The proteolytic activity of factor D (2.17 unit/mg/h) on this substrate was estimated to be 10(-5)-fold that of trypsin (2.18 x 10(5) unit/mg/h). The activities of factor D on other synthetic substrates were lower. Thus the proteolytic activity of factor D is considered to be very specific for its natural substrate, complement factor B bound with C3b, even when it is highly accumulated in vivo. The inhibitory effects of some serine protease inhibitors used clinically (nafamostat mesilate, sepinostat mesilate, camostat mesilate and gabexate mesilate) on the proteolytic activity of factor D on its natural substrate, factor B, were also investigated. Of these synthetic compounds, nafamostat mesilate was the most effective inhibitor (ID50:25 microM) of the activity of factor D on factor B.
Inagi
R
R
Department of Bacteriology, Osaka University Medical School, Japan.
Miyata
T
T
Oda
O
O
Maeda
K
K
Inoue
K
K
D000595:Amino Acid Sequence; D011416:Complement Factor D / Q000378:metabolism* / Q000652:urine; D005069:Evaluation Studies as Topic; D006461:Hemolysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000652:urine; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D006435:Renal Dialysis; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000652:urine; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C493488:CFD protein, human; D011416:Complement Factor D