title: Macrophage/microglia activation factor expression is restricted to lesion-associated microglial cells after brain trauma.
abstract: After traumatic brain lesion, microglial cells are rapidly activated, migrate toward the sites of injury, and cause secondary damage that accounts for most of the loss of brain function. In the present study, we have characterized a new macrophage/microglia activation factor (MAF). Using the monocytic cell line U937, we were able to demonstrate that MAF is upregulated after TPA-induced differentiation into macrophages. We have generated a specific antibody against MAF. In BV-2 microglial cells, MAF is partially co-localized with IB4, a classical microglial marker. In addition, we have analyzed the in vivo expression patterns of MAF after entorhinal cortex lesion. We were able to show a substantial upregulation of MAF on selected CD11b(+) and IB4(+) macrophages/microglial cells in the deafferented hippocampus and in the perilesional region, while no MAF expression was detectable on the contralateral side. Confocal microscopy revealed a lysosome-like expression pattern in BV-2 cells, as well as in ECL-associated macrophages/microglial cells in vivo. Furthermore, we were able to demonstrate that U937 cells with downregulated MAF converted slower and to a significantly reduced extent to the macrophageal phenotype after TPA treatment. In addition, MAF downregulation in BV-2 microglial cells substantially reduced the phagocytotic uptake of dextran beads. Our data indicate that MAF is expressed in selected macrophages/microglial cells around the lesion and in the degenerating hippocampus after ECL. Furthermore, MAF expression in monocytic cells seems to play a functional role in the differentiation to a phagocytosing phenotype and may be, at least partially, required for phagocytotic activity, specifically in lesioned tissue after brain trauma.
authors.affiliation: Center for Anatomy, Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Humboldt University, 10098 Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Lünemann
authors.forename: Oliver
authors.initials: O
authors.lastname: Ullrich
authors.forename: Antje
authors.initials: A
authors.lastname: Diestel
authors.forename: Thomas
authors.initials: T
authors.lastname: Jöns
authors.forename: Olaf
authors.initials: O
authors.lastname: Ninnemann
authors.forename: Adam
authors.initials: A
authors.lastname: Kovac
authors.forename: Elena E
authors.initials: EE
authors.lastname: Pohl
authors.forename: Ralf
authors.initials: R
authors.lastname: Hass
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
authors.forename: Sven
authors.initials: S
authors.lastname: Hendrix
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D037102:Lectins / Q000378:metabolism; D016215:Macrophage-Activating Factors / Q000096:biosynthesis*; D017628:Microglia / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D018613:Microscopy, Confocal; D015388:Organelles / Q000648:ultrastructure; D011817:Rabbits; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D039481:CD11b Antigen; C496198:IB4-saporin conjugate; D037102:Lectins; D016215:Macrophage-Activating Factors; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins