title: Traumatic brain injury induces macrophage subsets in the brain.
abstract: Traumatic brain injury (TBI) elicits innate inflammatory responses that can lead to secondary brain injury. To better understand the mechanisms involved in TBI-induced inflammation, we examined the nature of macrophages responding to TBI in mice. In this model, brain macrophages were increased >20-fold the day after injury and >77-fold 4 days after injury in the ipsilateral hemisphere compared with sham controls. TBI macrophage subsets were identified by using a reporter mouse strain (YARG) that expresses eYFP from an internal ribosome entry site (IRES) inserted at the 3' end of the gene for arginase-1 (Arg1), a hallmark of alternatively activated (M2) macrophages. One day after TBI, 21 ± 1.5% of ipsilateral brain macrophages expressed relatively high levels of Arg1 as detected by yellow fluorescent protein, and this subpopulation declined thereafter. Arg1(+) cells localized with macrophages near the TBI lesion. Gene expression analysis of sorted Arg1(+) and Arg1(-) brain macrophages revealed that both populations had profiles that included features of conventional M2 macrophages and classically activated (M1) macrophages. The Arg1(+) cells differed from Arg1(-) cells in multiple aspects, most notably in their chemokine repertoires. Thus, the macrophage response to TBI initially involves heterogeneous polarization toward at least two major subsets.
authors: San Francisco VA Medical Center, San Francisco, CA, USA. christine.hsieh@ucsf.edu
authors: Christine L
authors: CL
authors: Hsieh
authors: Charles C
authors: CC
authors: Kim
authors: Bryan E
authors: BE
authors: Ryba
authors: Erene C
authors: EC
authors: Niemi
authors: Jennifer K
authors: JK
authors: Bando
authors: Richard M
authors: RM
authors: Locksley
authors: Jialing
authors: J
authors: Liu
authors: Mary C
authors: MC
authors: Nakamura
authors: William E
authors: WE
authors: Seaman
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D001921:Brain / Q000276:immunology*; D001930:Brain Injuries / Q000276:immunology*; D002465:Cell Movement; D018925:Chemokines / Q000096:biosynthesis; D020869:Gene Expression Profiling; D007249:Inflammation / Q000276:immunology; D008164:Luminescent Proteins / Q000235:genetics; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018925:Chemokines; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: Alternative activation; Inflammation; Macrophage; Traumatic brain injury
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