Calreticulin is an abundant intracellular protein which is involved in a number of cellular functions. During cytomegalovirus infection, as well as inflammatory episodes in autoimmune disease, calreticulin can be released from cells and detected in the circulation, where it may act as an immunodominant autoantigen in diseases such as systemic lupus erythematosus. Calreticulin is known to bind to the molecules of innate immunity, such as C1q, the first subcomponent of complement. However, the functional implications of C1q–calreticulin interactions are unknown. In the present study we sought to investigate, in greater detail, the interaction between these two proteins following the release of calreticulin from neutrophils upon stimulation. In order to pinpoint the regions of interaction, recombinant calreticulin and its discrete domains (N-, P- and C-domains) were produced in Escherichia coli. Both the N- and P-domains of calreticulin were shown to bind to the globular head regions of C1q. Calreticulin also appeared to alter C1q-mediated immune functions. Binding of calreticulin to C1q inhibited haemolysis of IgM-sensitized erythrocytes. Both the N- and P-domains of calreticulin were found to contain sites involved in the inhibition of C1q-induced haemolysis. Full-length calreticulin, and its N- and P-domains, were also able to reduce the C1q-dependent binding of immune complexes to neutrophils. We conclude that calreticulin, once released from neutrophils during inflammation, may not only induce an antigenic reaction, but, under defined conditions, may also interfere with C1q-mediated inflammatory processes.
Skip Nav Destination
Article navigation
March 1997
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Research Article|
March 01 1997
Release of calreticulin from neutrophils may alter C1q-mediated immune functions
Uday KISHORE;
Uday KISHORE
*MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.
Search for other works by this author on:
Richard D. SONTHEIMER;
Richard D. SONTHEIMER
†Department of Dermatology & Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.
Search for other works by this author on:
Kedar N. SASTRY;
Kedar N. SASTRY
‡Department of Pathology, Boston University School of Medicine, Boston, MA, U.S.A.
Search for other works by this author on:
Ken S. ZANER;
Ken S. ZANER
‡Department of Pathology, Boston University School of Medicine, Boston, MA, U.S.A.
Search for other works by this author on:
Eugene. G. ZAPPI;
Eugene. G. ZAPPI
†Department of Dermatology & Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.
Search for other works by this author on:
Graham R. V. HUGHES;
Graham R. V. HUGHES
§The Rayne Institute, St. Thomas' Hospital, London, U.K.
Search for other works by this author on:
Munther A. KHAMASHTA;
Munther A. KHAMASHTA
§The Rayne Institute, St. Thomas' Hospital, London, U.K.
Search for other works by this author on:
Peter STRONG;
Peter STRONG
*MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.
Search for other works by this author on:
Kenneth B. M. REID;
Kenneth B. M. REID
*MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.
Search for other works by this author on:
Paul EGGLETON
Paul EGGLETON
¶
*MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.
¶To whom correspondence should be addressed.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 24 1996
Revision Received:
October 17 1996
Accepted:
November 07 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1997
1997
Biochem J (1997) 322 (2): 543–550.
Article history
Received:
July 24 1996
Revision Received:
October 17 1996
Accepted:
November 07 1996
Citation
Uday KISHORE, Richard D. SONTHEIMER, Kedar N. SASTRY, Ken S. ZANER, Eugene. G. ZAPPI, Graham R. V. HUGHES, Munther A. KHAMASHTA, Peter STRONG, Kenneth B. M. REID, Paul EGGLETON; Release of calreticulin from neutrophils may alter C1q-mediated immune functions. Biochem J 1 March 1997; 322 (2): 543–550. doi: https://doi.org/10.1042/bj3220543
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.