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Immature monocytes recruited to the ischemic mouse brain differentiate into macrophages with features of alternative activation.
Immature monocytes recruited to the ischemic mouse brain differentiate into macrophages with features of alternative activation.
- Source :
-
Brain, behavior, and immunity [Brain Behav Immun] 2016 Mar; Vol. 53, pp. 18-33. Date of Electronic Publication: 2015 Aug 12. - Publication Year :
- 2016
-
Abstract
- Acute stroke induces a local inflammatory reaction causing leukocyte infiltration. Circulating monocytes are recruited to the ischemic brain and become tissue macrophages morphologically indistinguishable from reactive microglia. However, monocytes are a heterogeneous population of cells with different functions. Herein, we investigated the infiltration and fate of the monocyte subsets in a mouse model of focal brain ischemia by permanent occlusion of the distal portion of the middle cerebral artery. We separated two main subtypes of CD11b(hi) monocytes according to their expression of the surface markers Ly6C and CD43. Using adoptive transfer of reporter monocytes and monocyte depletion, we identified the pro-inflammatory Ly6C(hi)CD43(lo)CCR2(+) subset as the predominant monocytes recruited to the ischemic tissue. Monocytes were seen in the leptomeninges from where they entered the cortex along the penetrating arterioles. Four days post-ischemia, they had invaded the infarcted core, where they were often located adjacent to blood vessels. At this time, Iba-1(-) and Iba-1(+) cells in the ischemic tissue incorporated BrdU, but BrdU incorporation was rare in the reporter monocytes. The monocyte phenotype progressively changed by down-regulating Ly6C, up-regulating F4/80, expressing low or intermediate levels of Iba-1, and developing macrophage morphology. Moreover, monocytes progressively acquired the expression of typical markers of alternatively activated macrophages, like arginase-1 and YM-1. Collectively, the results show that stroke mobilized immature pro-inflammatory Ly6C(hi)CD43(lo) monocytes that acutely infiltrated the ischemic tissue reaching the core of the lesion. Monocytes differentiated to macrophages with features of alternative activation suggesting possible roles in tissue repair during the sub-acute phase of stroke.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Adoptive Transfer
Animals
Brain Ischemia metabolism
Brain Ischemia pathology
Brain Ischemia therapy
Cell Differentiation immunology
Disease Models, Animal
Leukocyte Count
Macrophages immunology
Macrophages metabolism
Macrophages pathology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microglia metabolism
Microglia pathology
Monocytes metabolism
Monocytes pathology
Monocytes transplantation
Random Allocation
Receptors, CCR2 metabolism
Stroke immunology
Stroke metabolism
Stroke pathology
Stroke therapy
Brain Ischemia immunology
Microglia immunology
Monocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2139
- Volume :
- 53
- Database :
- MEDLINE
- Journal :
- Brain, behavior, and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 26275369
- Full Text :
- https://doi.org/10.1016/j.bbi.2015.08.010