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Protein & Cell

, Volume 1, Issue 2, pp 174–187 | Cite as

The class A macrophage scavenger receptor type I (SR-AI) recognizes complement iC3b and mediates NF-κB activation

  • Jason W. K. Goh
  • Yen Seah Tan
  • Alister W. Dodds
  • Kenneth B. M. Reid
  • Jinhua LuEmail author
Research Article

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.

Keywords

SR-AI complement iC3b signalling 293T cells macrophage 

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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Jason W. K. Goh
    • 1
  • Yen Seah Tan
    • 1
  • Alister W. Dodds
    • 2
  • Kenneth B. M. Reid
    • 2
  • Jinhua Lu
    • 1
    • 3
    Email author
  1. 1.Department of Microbiology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  2. 2.MRC Immunochemistry Unit, Department of BiochemistryUniversity of OxfordOxfordUK
  3. 3.Immunology ProgrammeNational University of SingaporeSingaporeSingapore

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