The Journal of Experimental Medicine
CSHL 2010 Immunology Conference
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 17 September 2001. doi:10.1084/jem.194.6.747
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 131K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Manderson, A. P.
Right arrow Articles by Parish, C. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Manderson, A. P.
Right arrow Articles by Parish, C. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2001/9/747/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 6, September 17, 2001 747-756

Original Article

Continual Low-Level Activation of the Classical Complement Pathway

Anthony P. Mandersona, Matthew C. Pickeringb, Marina Bottob, Mark J. Walportb, and Christopher R. Parisha

a Division of Immunology and Cell Biology, John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia
b Rheumatology Section, Division of Medicine, Imperial College School of Medicine, London W12 ONN, UK
Division of Immunology and Cell Biology, John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia.61-2-6125259561-2-61252604

christopher.parish{at}anu.edu.au

There is evidence that the classical complement pathway may be activated via a "C1-tickover" mechanism, analogous to the C3-tickover of the alternative pathway. We have quantitated and characterized this pathway of complement activation. Analysis of freshly collected mouse and human plasma revealed that spontaneous C3 activation rapidly occurred with the generation of C3 fragments in the plasma. By the use of complement- and Ig-deficient mice it was found that C1q, C4, C2, and plasma Ig were all required for this spontaneous C3 activation, with the alternative complement pathway further amplifying C3 fragment generation. Study of plasma from a human with C1q deficiency before and after therapeutic C1q infusion confirmed the existence of a similar pathway for complement activation in humans. Elevated levels of plasma C3 were detected in mice deficient in complement components required for activation of either the classical or alternative complement pathways, supporting the hypothesis that there is continuous complement activation and C3 consumption through both these pathways in vivo. Blood stasis was found to stimulate C3 activation by classical pathway tick-over. This antigen-independent mechanism for classical pathway activation may augment activation of the complement system at sites of inflammation and infarction.

Key Words: innate immunity • alternative complement pathway • C3 tick-over • inflammation • deficiency

Abbreviations used in this paper: HRG, histidine-rich glycoprotein; IC, immune complex; MBL, mannose-binding lectin; MFI, mean fluorescence intensity; RAG, recombinase-activating gene.

© 2001 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS