title: Bipolar/rod-shaped microglia are proliferating microglia with distinct M1/M2 phenotypes.
abstract: Microglia are generally considered the resident immune cells in the central nervous system (CNS) that regulate the primary events of neuroinflammatory responses. Microglia also play key roles in repair and neurodegeneration of the CNS after injury. Recent studies showed that trains of bipolar/rod-shaped microglia align end-to-end along the CNS injury site during the initial recovery phase. However, the cellular characteristics of bipolar/rod-shaped microglia remain largely unknown. Here, we established a highly reproducible in vitro culture model system to enrich and characterize bipolar/rod-shaped microglia by simply generating multiple scratches on a poly-d-lysine/laminin-coated culture dish. Trains of bipolar/rod-shaped microglia formed and aligned along the scratches in a manner that morphologically resembled microglial trains observed in injured brain. These bipolar/rod-shaped microglia were highly proliferative and expressed various M1/M2 markers. Further analysis revealed that these bipolar/rod-shaped microglia quickly transformed into amoeboid microglia within 30 minutes of lipopolysaccharide treatment, leading to the upregulation of pro-inflammatory cytokine gene expression and the activation of Jak/Stat. In summary, our culture system provides a model to further characterize this highly dynamic cell type. We suggest that bipolar/rod-shaped microglia are crucial for repairing the damaged CNS and that the molecular mechanisms underlying their morphological changes may serve as therapeutic biomarkers.
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Wing Yip
authors.initials: WY
authors.lastname: Tam
authors.affiliation: 1] Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong [2] Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Tat Chee Avenue, Hong Kong [3] State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Hong Kong.
authors.forename: Chi Him Eddie
authors.initials: CH
authors.lastname: Ma
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007797:Laminin; D008070:Lipopolysaccharides; D050791:STAT Transcription Factors; D053612:Janus Kinases; D008239:Lysine