title: Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain inflammation and enhances inflammatory signaling during traumatic brain injury.
abstract: Immune cells have important roles during disease and are known to contribute to secondary, inflammation-induced injury after traumatic brain injury. To delineate the functional role of macrophages during traumatic brain injury, we depleted macrophages using transgenic CD11b-DTR mice and subjected them to controlled cortical impact. We found that macrophage depletion had no effect on lesion size assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion resulted in a robust increase in proinflammatory gene expression in both the ipsilateral and contralateral hemispheres after controlled cortical impact. Interestingly, this sizeable increase in inflammation did not affect lesion development. We also showed that macrophage depletion resulted in increased proinflammatory gene expression in the brain and kidney in the absence of injury. These data demonstrate that depletion of macrophages in CD11b-DTR mice can significantly modulate the inflammatory response during brain injury without affecting lesion formation. These data also reveal a potentially confounding inflammatory effect in CD11b-DTR mice that must be considered when interpreting the effects of macrophage depletion in disease models.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Frieler
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Sameera
authors.initials: S
authors.lastname: Nadimpalli
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Boland
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Xie
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Kooistra
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Jianrui
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Yutein
authors.initials: Y
authors.lastname: Chung
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Kae W
authors.initials: KW
authors.lastname: Cho
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA; Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Carey N
authors.initials: CN
authors.lastname: Lumeng
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA; Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Neurology, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Wang
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 E. Catherine St., 7708 Medical Science II, Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: rmort@umich.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Mortensen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D039481:CD11b Antigen / Q000235:genetics; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: D039481:CD11b Antigen; D066257:Heparin-binding EGF-like Growth Factor; D012333:RNA, Messenger
keywords: CD11b-DTR; Inflammation; Macrophage depletion; Traumatic brain injury