The participation of siglec-F receptor in microglia-glioma interactions
Gliomas are highly invasive brain tumors with the occurence of numerous microglial cells arround the tumor. The density of these cells positively correlates with the malignancy, invasiveness and grading of gliomas. Sialic acid-binding immunoglobulin superfamily lectins (Siglecs) are members of immunoglobulin superfamily that recognize sialic acid residues of glycoproteins. Siglecs have intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIM), implicating them in the suppression of immunoreceptor signaling. Siglec-F is a CD33-related Siglec that binds to 2.3-, 2.6- and weakly 2.8-linked sialic acid. We analysed distribution and function of sialic acids and their receptor, Siglec-F, in glioma-microglia interactions. We observed Siglec-F gene transcription and Siglec-F protein expression in cultured embryonic stem cells derived microglia as well as high level of sialic acids in the mouse glioma cell line GL261. Flow cytomety analysis showed that sialylated structures expressed at the plasma membrane of glioma cells are recognized by recombinant mouse Siglec-F/Fc chimera. Enzymatic desialylation of the glioma cells with endoneuraminidase and α-neuraminidase significantly decreased binding of Siglec-F protein. Our data demonstrate that activation of immunosuppressive Siglec-F receptor by sialic acids can modulate microglia activity and immune response against malignant cells.
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