Direct interaction between CD91 and C1q.
C1q-mediated removal of immune complexes and apoptotic cells plays an important role in tissue homeostasis and the prevention of autoimmune conditions. It has been suggested that C1q mediates phagocytosis of apoptotic cells through a receptor complex assembled from CD91 (alpha-2- macroglobulin receptor, or low-density lipoprotein receptor-related protein) and calreticulin, with CD91 being the transmembrane part and calreticulin acting as the C1q-binding molecule. In the present study, we observe that C1q binds cells from a CD91 expressing monocytic cell line as well as monocytes from human blood. C1q binding to monocytes was shown to be correlated with CD91 expression and could be inhibited by the CD91 chaperone, receptor-associated protein. We also report data showing a direct interaction between CD91 and C1q. The interaction was investigated using various protein interaction assays. A direct interaction between purified C1q and CD91 was observed both by ELISA and a surface plasmon resonance assay, with either C1q or CD91 immobilized. The interaction showed characteristics of specificity because it was time-dependent, saturable and could be inhibited by known ligands of both CD91 and C1q. The results obtained show for the first time that CD91 recognizes C1q directly. On the basis of these findings, we propose that CD91 is a receptor for C1q and that this multifunctional scavenger receptor uses a subset of its ligand-binding sites for clearance of C1q and C1q bound material.
Duus
Karen
K
Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
Hansen
Erik W
EW
Tacnet
Pascale
P
Frachet
Philippe
P
Arlaud
Gerard J
GJ
Thielens
Nicole M
NM
Houen
Gunnar
G
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D037282:Calreticulin / Q000378:metabolism; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D013997:Time Factors
D015703:Antigens, CD; D037282:Calreticulin; C475476:LRP1 protein, human; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D015922:Complement C1q