Monomeric C-reactive protein modulates classic complement activation on necrotic cells
(2011) In FASEB Journal 25(12). p.4198-4210- Abstract
- The acute-phase protein C-reactive protein (CRP) recruits C1q to the surface of damaged cells and thereby initiates complement activation. However, CRP also recruits complement inhibitors, such as C4b-binding protein (C4bp) and factor H, which both block complement progression at the level of C3 and inhibits inflammation. To define how CRP modulates the classic complement pathway, we studied the interaction of CRP with the classic pathway inhibitor C4bp. Monomeric CRP (mCRP), but not pentameric CRP (pCRP), binds C4bp and enhances degradation of C4b and C3b. Both C1q, the initiator, and C4bp, the inhibitor of the classic pathway, compete for mCRP binding, and this competition adjusts the local balance of activation and inhibition. After... (More)
- The acute-phase protein C-reactive protein (CRP) recruits C1q to the surface of damaged cells and thereby initiates complement activation. However, CRP also recruits complement inhibitors, such as C4b-binding protein (C4bp) and factor H, which both block complement progression at the level of C3 and inhibits inflammation. To define how CRP modulates the classic complement pathway, we studied the interaction of CRP with the classic pathway inhibitor C4bp. Monomeric CRP (mCRP), but not pentameric CRP (pCRP), binds C4bp and enhances degradation of C4b and C3b. Both C1q, the initiator, and C4bp, the inhibitor of the classic pathway, compete for mCRP binding, and this competition adjusts the local balance of activation and inhibition. After attachment of pCRP to the surface of necrotic rat myocytes, generation of mCRP was demonstrated over a period of 18 h. Similarly, a biological role for mCRP, C1q, and C4bp in the disease setting of acute myocardial infarction was revealed. In this inflamed tissue, mCRP, pCRP, C4bp, C1q, and C4d were detected in acetone-fixed and in unfixed tissue. Protein levels were enhanced 6 h to 5 d after infarction. Thus, mCRP bound to damaged cardiomyocytes recruits C1q to activate and also C4bp to control the classic complement pathway.-Mihlan, M., Blom, A. M., Kupreishvili, K., Lauer, N., Stelzner, K., Bergstro " m, F., Niessen, H. W. M., Zipfel, P. F. Monomeric C-reactive protein modulates classic complement activation on necrotic cells. FASEB J. 25, 4198-4210 (2011). www.fasebj.org (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2333194
- author
- Mihlan, Michael ; Blom, Anna LU ; Kupreishvili, Koba ; Lauer, Nadine ; Stelzner, Kristin ; Mohlin, Frida LU ; Niessen, Hans W. M. and Zipfel, Peter F.
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cell death, C1q, C4b-binding protein, myocardial infarction
- in
- FASEB Journal
- volume
- 25
- issue
- 12
- pages
- 4198 - 4210
- publisher
- Wiley
- external identifiers
-
- wos:000298138100013
- scopus:82655181511
- pmid:21856781
- ISSN
- 1530-6860
- DOI
- 10.1096/fj.11-186460
- language
- English
- LU publication?
- yes
- id
- ee0877ad-75f6-422b-9ddd-e99ec0e37d36 (old id 2333194)
- date added to LUP
- 2016-04-01 13:36:01
- date last changed
- 2023-09-03 02:05:31
@article{ee0877ad-75f6-422b-9ddd-e99ec0e37d36, abstract = {{The acute-phase protein C-reactive protein (CRP) recruits C1q to the surface of damaged cells and thereby initiates complement activation. However, CRP also recruits complement inhibitors, such as C4b-binding protein (C4bp) and factor H, which both block complement progression at the level of C3 and inhibits inflammation. To define how CRP modulates the classic complement pathway, we studied the interaction of CRP with the classic pathway inhibitor C4bp. Monomeric CRP (mCRP), but not pentameric CRP (pCRP), binds C4bp and enhances degradation of C4b and C3b. Both C1q, the initiator, and C4bp, the inhibitor of the classic pathway, compete for mCRP binding, and this competition adjusts the local balance of activation and inhibition. After attachment of pCRP to the surface of necrotic rat myocytes, generation of mCRP was demonstrated over a period of 18 h. Similarly, a biological role for mCRP, C1q, and C4bp in the disease setting of acute myocardial infarction was revealed. In this inflamed tissue, mCRP, pCRP, C4bp, C1q, and C4d were detected in acetone-fixed and in unfixed tissue. Protein levels were enhanced 6 h to 5 d after infarction. Thus, mCRP bound to damaged cardiomyocytes recruits C1q to activate and also C4bp to control the classic complement pathway.-Mihlan, M., Blom, A. M., Kupreishvili, K., Lauer, N., Stelzner, K., Bergstro " m, F., Niessen, H. W. M., Zipfel, P. F. Monomeric C-reactive protein modulates classic complement activation on necrotic cells. FASEB J. 25, 4198-4210 (2011). www.fasebj.org}}, author = {{Mihlan, Michael and Blom, Anna and Kupreishvili, Koba and Lauer, Nadine and Stelzner, Kristin and Mohlin, Frida and Niessen, Hans W. M. and Zipfel, Peter F.}}, issn = {{1530-6860}}, keywords = {{cell death; C1q; C4b-binding protein; myocardial infarction}}, language = {{eng}}, number = {{12}}, pages = {{4198--4210}}, publisher = {{Wiley}}, series = {{FASEB Journal}}, title = {{Monomeric C-reactive protein modulates classic complement activation on necrotic cells}}, url = {{http://dx.doi.org/10.1096/fj.11-186460}}, doi = {{10.1096/fj.11-186460}}, volume = {{25}}, year = {{2011}}, }