Interactions of histidine-rich glycoprotein with immunoglobulins and proteins of the complement system.
Research output: Contribution to journal › Article
This study describes how the serum protein histidine-rich glycoprotein (HRG) affects the complement system. We show that HRG binds strongly to several complement proteins: C1q, factor H and C4b-binding protein and that it is found complexed with these proteins in human sera and synovial fluids of rheumatoid arthritis patients. HRG also binds C8 and to a lesser extent mannose-binding lectin, C4 and C3. However, HRG alone neither activates nor inhibits complement. Both HRG and C1q bind to necrotic cells and increase their phagocytosis. We found that C1q competes weakly with HRG for binding to necrotic cells whilst HRG does not compete with C1q. Furthermore, HRG enhances complement activation on necrotic cells measured as deposition of C3b. We show that HRG inhibits the formation of immune complexes of ovalbumin/anti-ovalbumin, whilst the reverse holds for C1q. Immune complexes formed in the presence of HRG show enhanced complement activation, whilst those formed in the presence of C1q show diminished complement activation. Taken together, HRG may assist in the maintenance of normal immune function by mediating the clearance of necrotic material, inhibiting the formation of insoluble immune complexes and enhancing their ability to activate complement, resulting in faster clearance.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Publication status||Published - 2009|
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Protein Chemistry (013017510), Cell and Matrix Biology (LUR000002), Department of Dermatology and Venereology (Lund) (013006000), Department of Rheumatology (013036000), Connective Tissue Biology (013230151)