| Autor: |
McRae JL; Department of Nephrology, Immunology Research Centre, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia. Jennifer.MCRAE@svhm.org.au, Duthy TG, Griggs KM, Ormsby RJ, Cowan PJ, Cromer BA, McKinstry WJ, Parker MW, Murphy BF, Gordon DL |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2005 May 15; Vol. 174 (10), pp. 6250-6. |
| DOI: |
10.4049/jimmunol.174.10.6250 |
| Abstrakt: |
Factor H-related protein 5 (FHR-5) is a recently discovered member of the factor H (fH)-related protein family. FHR proteins are structurally similar to the complement regulator fH, but their biological functions remain poorly defined. FHR-5 is synthesized in the liver and consists of 9 short consensus repeats (SCRs), which display various degrees of homology to those of fH and the other FHR proteins. FHR-5 colocalizes with complement deposits in vivo and binds C3b in vitro, suggesting a role in complement regulation or localization. The current study examined whether rFHR-5 exhibits properties similar to those of fH, including heparin binding, CRP binding, cofactor activity for the factor I-mediated degradation of C3b and decay acceleration of the C3 convertase. rFHR-5 bound heparin-BSA and heparin-agarose and a defined series of truncations expressed in Pichia pastoris localized the heparin-binding region to within SCRs 5-7. rFHR-5 bound CRP, and this binding was also localized to SCRs 5-7. FHR-5 inhibited alternative pathway C3 convertase activity in a fluid phase assay; however, dissociation of the convertase was not observed in a solid phase assay. rFHR-5 displayed factor I-dependent cofactor activity for C3b cleavage, although it was apparently less effective than fH. In addition, we demonstrate association of FHR-5 with high density lipid lipoprotein complexes in human plasma. These results demonstrate that FHR-5 shares properties of heparin and CRP binding and lipoprotein association with one or more of the other FHRs but is unique among this family of proteins in possessing independent complement-regulatory activity. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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