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      Evaluation of the Proteolytic Activity of Factor D Accumulated as an Active Serine Protease in Patients with Chronic Renal Failure

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          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<sup>–5</sup>-fold that of trypsin (2.18 × 10<sup>5</sup> 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 (ID<sub>50</sub>:25 µ M) of the activity of factor D on factor B.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1994
          1994
          16 December 2008
          : 66
          : 3
          : 285-290
          Affiliations
          aDepartment of Bacteriology, Osaka University Medical School, Osaka, bDepartment of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, and cBio-Dynamics Research Institute, Nagoya, Japan
          Article
          187824 Nephron 1994;66:285–290
          10.1159/000187824
          8190180
          © 1994 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 6
          Categories
          Original Paper

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