title: Siglec-h on activated microglia for recognition and engulfment of glioma cells.
abstract: 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.
authors: Neural Regeneration Group, Institute of Reconstructive Neurobiology, Medical Faculty, University Bonn, Bonn, Germany.
authors: Jens
authors: J
authors: Kopatz
authors: Clara
authors: C
authors: Beutner
authors: Kristian
authors: K
authors: Welle
authors: Liviu G
authors: LG
authors: Bodea
authors: Julia
authors: J
authors: Reinhardt
authors: Janine
authors: J
authors: Claude
authors: Bettina
authors: B
authors: Linnartz-Gerlach
authors: Harald
authors: H
authors: Neumann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000166:cytology; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D003412:Cricetulus; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000235:genetics; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D063267:Sialic Acid Binding Ig-like Lectin 1; D007371:Interferon-gamma