%A Paetau,Sonja %A Rolova,Taisia %A Ning,Lin %A Gahmberg,Carl G. %D 2017 %J Frontiers in Molecular Neuroscience %C %F %G English %K ICAM-5,Microglia,Adhesion,Phagocytosis,TNF-α,Integrins,ICAM-1,IL-10 %Q %R 10.3389/fnmol.2017.00431 %W %L %M %P %7 %8 2017-December-22 %9 Original Research %+ Carl G. Gahmberg,Laboratory of CG Gahmberg, Division of Biochemistry and Biotechnology, Department of Biosciences, University of Helsinki,Finland,carl.gahmberg@helsinki.fi %# %! Neuronal ICAM-5 regulates microglia functions %* %< %T Neuronal ICAM-5 Inhibits Microglia Adhesion and Phagocytosis and Promotes an Anti-inflammatory Response in LPS Stimulated Microglia %U https://www.frontiersin.org/articles/10.3389/fnmol.2017.00431 %V 10 %0 JOURNAL ARTICLE %@ 1662-5099 %X The intercellular adhesion molecule-5 (ICAM-5) regulates neurite outgrowth and synaptic maturation. ICAM-5 overexpression in the hippocampal neurons induces filopodia formation in vitro. Since microglia are known to prune supernumerous synapses during development, we characterized the regulatory effect of ICAM-5 on microglia. ICAM-5 was released as a soluble protein from N-methyl-D-aspartic acid (NMDA)-treated neurons and bound by microglia. ICAM-5 promoted down-regulation of adhesion and phagocytosis in vitro. Microglia formed large cell clusters on ICAM-5-coated surfaces whereas they adhered and spread on the related molecule ICAM-1. ICAM-5 further reduced the secretion of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), but on the contrary induced the secretion of the anti-inflammatory IL-10 from lipopolysaccharide (LPS) stimulated microglia. Thus, ICAM-5 might be involved in the regulation of microglia in both health and disease, playing an important neuroprotective role when the brain is under immune challenges and as a “don’t-eat-me” signal when it is solubilized from active synapses.