期刊
PROTEIN & CELL
卷 1, 期 2, 页码 174-187出版社
HIGHER EDUCATION PRESS
DOI: 10.1007/s13238-010-0020-3
关键词
SR-AI; complement; iC3b; signalling; 293T cells; macrophage
类别
资金
- Singapore Biomedical Research Council [R-182-000-089-305]
- National Medical Research Council [R-364-000-019-213]
- National University of Singapore
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 DH5 alpha, leading to NF-kappa B activation and IL-8 production. However, this requires E. coli DH5 alpha 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 DH5a and blocks DH5a 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 DH5 alpha. These results revealed a novel property of SR-AI as a complement receptor for iC3b-opsonized bacteria that can elicit cell signaling.
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