Fc gamma receptor-mediated phagocytosis pathway (FcγR-mediated phagocytosis)

The Fc gamma receptor-mediated phagocytosis pathway is a critical immunological process in macrophages and monocytes that enables the recognition and ingestion of IgG-opsonized particles (KEGG: map04666). This pathway is initiated when the Fc region of an IgG antibody binds to Fc gamma receptors (FcγRs) on the cell surface, such as FcγRI (CD64), FcγRIIA (CD32a), or FcγRIIIA (CD16a) (Nature Reviews Immunology, 2010). Binding triggers the phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) by Src-family kinases, which subsequently recruit and activate Spleen Tyrosine Kinase (SYK) (Journal of Biological Chemistry, 2002). SYK activation leads to a downstream signaling cascade involving PI3K, PLCγ, and Rho GTPases (Rac and Cdc42), which coordinate the actin cytoskeleton to form a phagocytic cup and engulf the target (Cell Communication and Signaling, 2014). In oncology, this pathway is the primary mechanism for antibody-dependent cellular phagocytosis (ADCP), where therapeutic monoclonal antibodies like Rituximab or Trastuzumab mark tumor cells for destruction (Frontiers in Immunology, 2019). Conversely, inhibitors of pathway components, such as the SYK inhibitor Fostamatinib, are used to treat autoimmune conditions like immune thrombocytopenia by preventing the phagocytic clearance of self-antigens (New England Journal of Medicine, 2018).

Other names

Fc-gamma receptor signalingIgG-mediated phagocytosisAntibody-dependent cellular phagocytosisADCP pathway

The pathway is modulated by inhibiting intracellular signaling molecules like SYK to treat autoimmunity or by using monoclonal antibodies to trigger receptor-mediated engulfment of target cells in cancer therapy.