Evaluation of the proteolytic activity of factor D accumulated as an active serine protease in patients with chronic renal failure

R. Inagi, T. Miyata, O. Oda, K. Maeda, K. Inoue

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 105 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 μM) of the activity of factor D on factor B.

Original languageEnglish
Pages (from-to)285-290
Number of pages6
JournalNephron
Volume66
Issue number3
Publication statusPublished - 1994 Jan 1
Externally publishedYes

Keywords

  • Chronic renal failure
  • Factor D
  • Proteolytic activity
  • Serine protease inhibitor
  • Synthetic peptide substrates

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Urology
  • Physiology (medical)

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