A classical function of Clq is to bind immune complexes and initiate complement activation producing membrane lytic complexes, opsonins and anaphylatoxins. This classical pathway of complement activation is also elici...A classical function of Clq is to bind immune complexes and initiate complement activation producing membrane lytic complexes, opsonins and anaphylatoxins. This classical pathway of complement activation is also elicited when Clq binds some other ligands. Besides complement activation, Clq also regulates cell differentiation, adhesion, migration, activation and survival. Clq deficiency is associated with autoimmunity as well as increased susceptibility to infections. In this article, we discuss the basic properties of Clq, its expression, and classical and regulatory functions. Cellular ＆ Molecular Immunology.展开更多
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,inves...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 293T cells,SR-AI could respond to E.coli DH5α,leading to NF-κB activation and IL-8 production.However,this requires E.coli DH5αto 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 DH5αand blocks DH5αstimulation 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.展开更多
文摘A classical function of Clq is to bind immune complexes and initiate complement activation producing membrane lytic complexes, opsonins and anaphylatoxins. This classical pathway of complement activation is also elicited when Clq binds some other ligands. Besides complement activation, Clq also regulates cell differentiation, adhesion, migration, activation and survival. Clq deficiency is associated with autoimmunity as well as increased susceptibility to infections. In this article, we discuss the basic properties of Clq, its expression, and classical and regulatory functions. Cellular ＆ Molecular Immunology.
基金This project is support by the Singapore Biomedical Research Council grant R-182-000-089-305National Medical Research Council grants R-364-000-019-213.JWKG received a scholarship from the National University of Singapore.
文摘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 293T cells,SR-AI could respond to E.coli DH5α,leading to NF-κB activation and IL-8 production.However,this requires E.coli DH5αto 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 DH5αand blocks DH5αstimulation 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.
