Abstract: Background: Leukocytes express Fcγ receptors, which are specific for the constant region of immunoglobulin G. Aggregation of these receptors activates a repertoire of responses that can lead to targeted cell killing by antibody directed cellular cytotoxicity. The nature of the myeloid response to Fcγ receptor aggregation is highly variable and depends on the maturation state of the cell, but little is known about the signalling mechanisms underlying this variability.Results: We show here that differentiation of a monocytic cell line, U937, to a more macrophage phenotype resulted in an absolute and fundamental switch in the nature of the phospholipid signalling pathway recruited following Fcγ receptor aggregation. In cytokine-primed monocytes, aggregation of the high-affinity receptor FcγRI resulted in the activation of phospholipase D and sphingosine kinase, which in turn led to the transient release of stored calcium; these effects were mediated by the γ chain, an FcγRI accessory protein. In contrast, in cells differentiated to a more macrophage type, aggregation of FcγRI resulted in the FcγRIIa-mediated activation of phospholipase C, and the resulting calcium response was prolonged as calcium entry was stimulated.Conclusions: The switch in FcγRI signalling pathways upon monocyte differentiation is mediated by a switch in the accessory molecule recruited by FcγRI, which lacks its own intrinsic signal transduction motif. As many immune receptors have separate polypeptide chains for ligand binding and signal transduction (allowing a similar switch in signalling pathways), the mechanism described here is likely to be widely used.

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration

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{{Explor lien
   |wiki=    Sante
   |area=    MersV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     ISTEX:B24ED7113398FAB8F911958DF2F198CFB7B64BD9
   |texte=   A molecular switch changes the signalling pathway used by the FcγRI antibody receptor to mobilise calcium
}}