Advanced

Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation.

Holmér, Andreas LU ; Manderson, Gavin LU ; Mörgelin, Matthias LU ; Day, Anthony J; Heinegård, Dick LU and Blom, Anna LU (2009) In Molecular Immunology 46. p.830-839
Abstract
The extracellular matrix consists of structural macromolecules and other proteins with regulatory functions. An important family of the latter class of molecules found in most tissues is the small leucine-rich repeat proteins (SLRPs). We have previously shown that the SLRP fibromodulin binds directly to C1q and activates the classical pathway of complement. In the present study we further examine the interactions between SLRPs and complement. Osteoadherin, like fibromodulin, binds C1q and activates the classical pathway strongly while moderate activation is seen in the terminal pathway. This can be explained by the interaction of fibromodulin and osteoadherin with factor H, a major soluble inhibitor of complement. Also, chondroadherin was... (More)
The extracellular matrix consists of structural macromolecules and other proteins with regulatory functions. An important family of the latter class of molecules found in most tissues is the small leucine-rich repeat proteins (SLRPs). We have previously shown that the SLRP fibromodulin binds directly to C1q and activates the classical pathway of complement. In the present study we further examine the interactions between SLRPs and complement. Osteoadherin, like fibromodulin, binds C1q and activates the classical pathway strongly while moderate activation is seen in the terminal pathway. This can be explained by the interaction of fibromodulin and osteoadherin with factor H, a major soluble inhibitor of complement. Also, chondroadherin was found to bind C1q and activate complement, albeit to a lesser extent. Chondroadherin also binds factor H. We confirm published data showing that biglycan and decorin bind C1q but do not activate complement. In this study a similar pattern is seen for lumican although its affinity for C1q is lower than for biglycan and decorin. Furthermore, using electron microscopy and radiolabeled SLRPs, we demonstrate two different classes of SLRP binding sites on C1q, to head and stalk respectively, where only binding to the head appears to be activating. We propose a role for SLRPs in the regulation of complement activation in diseases involving the extracellular matrix, particularly those characterized by chronic inflammation such as rheumatoid arthritis, atherosclerosis, osteoarthritis and chronic obstructive lung disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Immunology
volume
46
pages
830 - 839
publisher
Pergamon
external identifiers
  • WOS:000263942200009
  • PMID:18962898
  • Scopus:59249103181
ISSN
1872-9142
DOI
10.1016/j.molimm.2008.09.018
language
English
LU publication?
yes
id
6a80ee31-ae67-4e39-99c3-5743785608c7 (old id 1261787)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18962898?dopt=Abstract
date added to LUP
2008-11-04 12:06:48
date last changed
2016-11-13 04:26:08
@misc{6a80ee31-ae67-4e39-99c3-5743785608c7,
  abstract     = {The extracellular matrix consists of structural macromolecules and other proteins with regulatory functions. An important family of the latter class of molecules found in most tissues is the small leucine-rich repeat proteins (SLRPs). We have previously shown that the SLRP fibromodulin binds directly to C1q and activates the classical pathway of complement. In the present study we further examine the interactions between SLRPs and complement. Osteoadherin, like fibromodulin, binds C1q and activates the classical pathway strongly while moderate activation is seen in the terminal pathway. This can be explained by the interaction of fibromodulin and osteoadherin with factor H, a major soluble inhibitor of complement. Also, chondroadherin was found to bind C1q and activate complement, albeit to a lesser extent. Chondroadherin also binds factor H. We confirm published data showing that biglycan and decorin bind C1q but do not activate complement. In this study a similar pattern is seen for lumican although its affinity for C1q is lower than for biglycan and decorin. Furthermore, using electron microscopy and radiolabeled SLRPs, we demonstrate two different classes of SLRP binding sites on C1q, to head and stalk respectively, where only binding to the head appears to be activating. We propose a role for SLRPs in the regulation of complement activation in diseases involving the extracellular matrix, particularly those characterized by chronic inflammation such as rheumatoid arthritis, atherosclerosis, osteoarthritis and chronic obstructive lung disease.},
  author       = {Holmér, Andreas and Manderson, Gavin and Mörgelin, Matthias and Day, Anthony J and Heinegård, Dick and Blom, Anna},
  issn         = {1872-9142},
  language     = {eng},
  pages        = {830--839},
  publisher    = {ARRAY(0x8138870)},
  series       = {Molecular Immunology},
  title        = {Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation.},
  url          = {http://dx.doi.org/10.1016/j.molimm.2008.09.018},
  volume       = {46},
  year         = {2009},
}