Imperial College London
Alternate

ProfessorMatthewPickering

Faculty of Medicine, Department of Immunology and Inflammation

Centre Director, Professor of Rheumatology
 
 
 
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Contact

 

matthew.pickering Website

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N12Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Renner:2016:10.4049/jimmunol.1500793,
author = {Renner, B and Tong, HH and Laskowski, J and Jonscher, K and Goetz, L and Woolaver, R and Hannan, J and Li, YX and Hourcade, D and Pickering, MC and Holers, VM and Thurman, JM},
doi = {10.4049/jimmunol.1500793},
journal = {Journal of Immunology},
pages = {1355--1365},
title = {Annexin A2 enhances complement activation by inhibiting factor H},
url = {http://dx.doi.org/10.4049/jimmunol.1500793},
volume = {196},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Factor H is a circulating protein that regulates activation of the alternative pathway (AP) of complement. Mutations and genetic variations of factor H are associated with several AP-mediated diseases, highlighting the critical role of factor H in AP regulation. AP-mediated inflammation is typically triggered by illness or tissue injury, however, and tissue injury can trigger AP activation in individuals with fully functional factor H. This suggests that factor H function is affected by local conditions within tissues. We hypothesized that inducible proteins impair the ability of factor H to locally control the AP, thereby increasing AP activation. We used purified murine factor H to immunoprecipitate binding partners from mouse kidneys. Using immunoaffinity liquid chromatography–mass spectrometry, we identified annexin A2 as a factor H binding partner. Further experiments showed that annexin A2 reduces the binding of factor H to cell surfaces. Recombinant annexin A2 impaired complement regulation by factor H and increased complement activation on renal cell surfaces in vitro and in vivo. In a murine model of acute pneumococcal otitis media, the administration of annexin A2 increased AP-mediated bacterial opsonization and clearance. In conclusion, the local production of annexin A2 within tissues suppresses regulation of the AP by factor H. Annexin A2 can contribute to AP-mediated tissue inflammation by locally impairing factor H function, but it can also improve complement-mediated bacterial clearance.
AU  - Renner,B
AU  - Tong,HH
AU  - Laskowski,J
AU  - Jonscher,K
AU  - Goetz,L
AU  - Woolaver,R
AU  - Hannan,J
AU  - Li,YX
AU  - Hourcade,D
AU  - Pickering,MC
AU  - Holers,VM
AU  - Thurman,JM
DO  - 10.4049/jimmunol.1500793
EP  - 1365
PY  - 2016///
SN  - 1550-6606
SP  - 1355
TI  - Annexin A2 enhances complement activation by inhibiting factor H
T2  - Journal of Immunology
UR  - http://dx.doi.org/10.4049/jimmunol.1500793
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000368596600042&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
VL  - 196
ER  -
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