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- W3048347902 abstract "CD47 acts as a “don’t eat me” signal that protects cells from phagocytosis by binding and activating its receptor SIPRA on macrophages. CD47 suppresses multiple different pro-engulfment “eat me” signals, including immunoglobulin G (IgG), complement, and calreticulin, on distinct target cells. This complexity has limited understanding of how the “don’t eat me” signal is transduced biochemically. Here, we utilized a reconstituted system with a defined set of signals to interrogate the mechanism of SIRPA activation and its downstream targets. CD47 ligation altered SIRPA localization, positioning SIRPA for activation at the phagocytic synapse. At the phagocytic synapse, SIRPA inhibited integrin activation to limit macrophage spreading across the surface of the engulfment target. Chemical reactivation of integrin bypassed CD47-mediated inhibition and rescued engulfment, similar to the effect of a CD47 function-blocking antibody. Thus, the CD47-SIRPA axis suppresses phagocytosis by inhibiting inside-out activation of integrin signaling in the macrophage, with implications to cancer immunotherapy applications." @default.
- W3048347902 created "2020-08-13" @default.
- W3048347902 creator A5048790407 @default.
- W3048347902 creator A5049281520 @default.
- W3048347902 creator A5091261902 @default.
- W3048347902 date "2020-08-01" @default.
- W3048347902 modified "2023-10-16" @default.
- W3048347902 title "CD47 Ligation Repositions the Inhibitory Receptor SIRPA to Suppress Integrin Activation and Phagocytosis" @default.
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- W3048347902 doi "https://doi.org/10.1016/j.immuni.2020.07.008" @default.
- W3048347902 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7453839" @default.
- W3048347902 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32768386" @default.
- W3048347902 hasPublicationYear "2020" @default.
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