The class A macrophage scavenger receptor type I (SR-AI) recognizes complement iC3b and mediates NF-κB activation.
10.1007/s13238-010-0020-3
- Author:
Jason W K GOH
1
;
Yen Seah TAN
;
Alister W DODDS
;
Kenneth B M REID
;
Jinhua LU
Author Information
1. Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
- Publication Type:Journal Article
- MeSH:
Amino Acid Sequence;
Carrier Proteins;
genetics;
metabolism;
Complement C3b;
metabolism;
Escherichia coli;
immunology;
HEK293 Cells;
Humans;
Macrophage Activation;
Molecular Sequence Data;
Mutagenesis;
NF-kappa B;
genetics;
metabolism;
Phagocytosis;
Serine-Arginine Splicing Factors;
Signal Transduction
- From:
Protein & Cell
2010;1(2):174-187
- CountryChina
- Language:English
-
Abstract:
The macrophage scavenger receptor SR-AI binds to host tissue debris to perform clearance and it binds to bacteria for phagocytosis. In addition, SR-AI modulates macrophage activation through cell signaling. However, investigation of SR-AI signaling on macrophages is complicated due to its promiscuous ligand specificity that overlaps with other macrophage receptors. Therefore, we expressed SR-AI on HEK 293T cells to investigate its ligand binding and signaling. On 293Tcells, SR-AI could respond to E. coli DH5α, leading to NF-κB activation and IL-8 production. However, this requires E. coli DH5α to be sensitized by fresh serum that is treated with heat-inactivation or complement C3 depletion. Anti-C3 antibody inhibits the binding of SR-AI to serum-sensitized DH5α and blocks DH5α stimulation of SR-AI signaling. Further analysis showed that SR-AI can directly bind to purified iC3b but not C3 or C3b. By mutagenesis, The SRCR domain of SR-AI was found to be essential in SR-AI binding to serum-sensitized DH5α. These results revealed a novel property of SR-AI as a complement receptor for iC3b-opsonized bacteria that can elicit cell signaling.
