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Siglec‐h on activated microglia for recognition and engulfment of glioma cells
Author(s) -
Kopatz Jens,
Beutner Clara,
Welle Kristian,
Bodea Liviu G.,
Reinhardt Julia,
Claude Janine,
LinnartzGerlach Bettina,
Neumann Harald
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22501
Subject(s) - siglec , microglia , biology , glioma , microbiology and biotechnology , phagocytosis , immunology , antibody , cancer research , inflammation
Sialic‐acid‐binding immunoglobulin‐like lectin‐h (Siglec‐h) is a recently identified mouse‐specific CD33‐related Siglec that signals via DAP12/TYROBP. Expression of Siglec‐h has been observed on plasmacytoid dendritic cells and microglia, but the ligand and the function of Siglec‐h remained elusive. Here, we demonstrate gene transcription and protein expression of Siglec‐h by mouse microglia after interferon‐γ treatment or polarization into a M1‐subtype. Microglial Siglec‐h acted as phagocytosis receptor since targeting of microsphere beads to Siglec‐h triggered their uptake into the microglia. The extracellular domain of Siglec‐h protein bound to mouse glioma lines, but not to astrocytes or other normal mouse cells. Microglial cells stimulated to express Siglec‐h engulfed intact glioma cells without prior induction of apoptosis and slightly reduced glioma cell number in culture. Phagocytosis of glioma cells by activated microglia was dependent on Siglec‐h and its adapter molecule DAP12. Thus, data show that M1‐polarized microglial cells can engulf glioma cells via a DAP12‐mediated Siglec‐h dependent mechanism.