title: A pivotal role of nonmuscle myosin II during microglial activation.
abstract: Microglia are resident macrophages in the central nervous system (CNS) and the primary cells that contribute to CNS inflammation in many pathological conditions. Upon any signs of brain damage, microglia become activated and undergo tremendous cellular reorganization to adopt appropriate phenotypes. They migrate to lesion areas, accumulate, phagocytose cells or cellular debris, and produce a large array of inflammatory mediators like cytokines, chemokines, reactive oxygen species, and other mediators. To cope with the extreme cellular rearrangements during activation, microglia have to be highly dynamic. One major component of the cytoskeleton in nonmuscle cells is nonmuscle myosin II (NM II). This study was aimed to examine the functional role of NM II in resting and activated microglia. Using immunohistochemistry, we demonstrate strong expression of NM II isoform B (NM IIB) in microglia during cuprizone-induced demyelination as well as in cultured microglia. Treatment with the NM II inhibitor blebbistatin prevented the morphological shaping of microglial cells, led to functional deficits during chemokine-directed migration and phagocytosis, induced NM IIB redistribution, and affected actin microfilament patterning. In addition, inhibition of NM II led to an attenuated release of nitric oxide (NO), while TNFα secretion was not altered. In conclusion, we propose a pivotal role of NM II in cytoskeleton organization during microglial activation. This is of great importance to understand the mechanisms of microglial action in inflammatory CNS diseases.
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Janßen
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gudi
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Chittappen K
authors.initials: CK
authors.lastname: Prajeeth
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Vikramjeet
authors.initials: V
authors.lastname: Singh
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Stahl
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Heckers
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Skripuletz
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Refik
authors.initials: R
authors.lastname: Pul
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Trebst
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsiavaliaris
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany. Electronic address: stangel.martin@mh-hannover.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D018995:Myosin Heavy Chains / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018932:Chemokine CCL2; D006576:Heterocyclic Compounds, 4 or More Rings; D008996:Monoamine Oxidase Inhibitors; C472645:blebbistatin; D003471:Cuprizone; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains
keywords: Cytoskeleton; Microglial response; NO production; Neuroinflammation; Nonmuscle myosin II