Background: Unlike most complement proteins, complement factor D is believed to be synthesized not by the liver but exclusively by adipose tissue. Method: Culture supernatants obtained from primary culture of normal human hepatocytes were assayed for factor D by ELISA and analyzed by Western blotting. Results: When normal hepatocytes were cultured in protein-free medium without addition of any stimulator for 5 days, factor D was detected in the supernatants at levels as high as 331.07 ± 41.38 μg/106 cells. Addition of TNF-α, IFN-γ, IL-1β or LPS to the medium did not result in any distinct effect on the amounts of secreted factor D. Reversible inhibition of factor D secretion by these cells was observed when cultured in the presence of cycloheximide. By immunoblot analysis, secreted factor D exhibited double bands, one with a molecular weight similar to factor D in normal human serum and the other with a slightly larger molecular weight. Conclusion: Normal human hepatocytes synthesize factor D constitutively. The liver may be a major source of plasma factor D.

Keywords:
Factor D, Complement synthesis, Hepatocytes
1.
Nilsson B, Ekdahl KN: Component of the alternative pathway; in Rother K, Till GO, Haensch GM (eds): The Complement System, ed 2. Berlin, Springer, 1998, pp 23–49.
2.
Morgan BP: Complement: Clinical Aspects and Relevance to Disease. London, Academic Press, 1990, pp 8–35.
3.
White RT, Damm D, Hancock N, Rosen BS, Lowell BB, Usher P, Flier JS, Spiegelman BM: Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. Biol Chem 1992;267:9210–9213.
4.
Choy LN, Rosen BS, Spiegelman BM: Adipsin and an endogenous pathway of complement from adipose cells. J Biol Chem 1992;267:12736–12741.
5.
Morgan BP, Gasque P: Extrahepatic complement biosynthesis: Where, when and why? Clin Exp Immunol 1997;107:1–7.
6.
Barnum SR, Volanakis JE: Biosynthesis of complement protein D by HepG2 cells: A comparison of D produced by HepG2 cells, U937 cells and blood monocytes. Eur J Immunol 1985;15:1148–1151.
7.
Barnum SR, Ishii Y, Agrawal A, Volanakis JE: Production and interferon-γ-mediated regulation of complement component C2 and factors B and D by astroglioma cell line U105-MG. Biochem J 1992;287:595–601.
8.
Whaley K: Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes. J Exp Med 1980;151:501–506.
9.
Miyama A, Kato T, Horai S: Trypsin-activated complex of human factor B with cobra venom factor (CVF), cleaving C3 and C5 and generating a lytic factor for unsensitized guinea pig erythrocytes. I. Generation of the activated complex. Biken J 1975;18:193–204.
10.
Whaley K, North J: Haemolytic assay for whole complement activity and individual components; in Dodds AW, Sim RB (eds): Complement. Oxford, IRL Press, 1997, pp 19–47.
11.
Kitano E, Kitamura H: Synthesis of the third component complement (C3) by human gastric cancer-derived cell lines. Clin Exp Immunol 1993;94:273–278.
12.
Andoh A, Fujiyama Y, Bamba T, Hosada S: Differential cytokine regulation of complement C3, C4 and factor B synthesis in human intestinal epithelial cell line Caco-2. J Immunol 1993;151:4239–4247.
13.
Yamauchi Y, Stevens JW, Macon KJ, Volanakis JE: Recombinant and native zymogen forms of human complement factor D. J Immunol 1994;152:3645–3653.
14.
Jing H, Macon KJ, Moore D, Delucas LJ, Volanakis JE, Narayana SVL: Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D. EMBO J 1999;18:804–814.
15.
Williams PL, Warwick R, Dyson M, Bannister LH (eds): The liver; in Gray’s Anatomy, ed 37. London, Churchill Livingston, 1989, pp 1384–1398.
16.
Pascual M, Steiger G, Estreicher L, Macon K, Volanakis JE, Schifferli JA: Metabolism of complement factor D in renal failure. Kidney Int 1988; 34:529–536.
© 2000 S. Karger AG, Basel
2000
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.