Macrophages prevent hemorrhagic infarct transformation in murine stroke models

Autor: Nico van Rooijen, Anne K. Mausberg, John-Ih Lee, Hans-Peter Hartung, Ioannis Simiantonakis, Michael Gliem, Sebastian Jander
Přispěvatelé: Molecular cell biology and Immunology, CCA - Immuno-pathogenesis
Rok vydání: 2012
Předmět:
CCR2
Pathology
Time Factors
Infarction
Brain ischemia
Mice
Antigens
Ly
Medicine
Diphtheria Toxin
Stroke
CD11b Antigen
Germanium
Drug Administration Routes
Cell Differentiation
Infarction
Middle Cerebral Artery
Hemorrhagic infarct
Flow Cytometry
medicine.anatomical_structure
Neurology
Intercellular Signaling Peptides and Proteins
Receptors
Chemokine
medicine.symptom
Intracranial Hemorrhages
Heparin-binding EGF-like Growth Factor
Brain Infarction
medicine.medical_specialty
Interferon Inducers
Receptors
CCR2
CX3C Chemokine Receptor 1
Antigens
Differentiation
Myelomonocytic
Mice
Transgenic
Inflammation
Motor Activity
Transforming Growth Factor beta1
Lesion
Antigens
CD
Organometallic Compounds
Animals
business.industry
Macrophages
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
Gene Expression Regulation
Leukocyte Common Antigens
Neurology (clinical)
Bone marrow
Intracranial Thrombosis
Propionates
business
Zdroj: Annals of Neurology, 71(6), 743-752. John Wiley and Sons Inc.
Gliem, M, Mausberg, A K, Lee, J I, Simiantonakis, I, van Rooijen, N, Hartung, H P & Jander, S 2012, ' Macrophages prevent hemorrhagic infarct transformation in murine stroke models ', Annals of Neurology, vol. 71, no. 6, pp. 743-752 . https://doi.org/10.1002/ana.23529
ISSN: 0364-5134
DOI: 10.1002/ana.23529
Popis: Objective: Inflammation is increasingly viewed as a new therapeutic target in subacute stages of brain infarction. However, apart from causing secondary damage, inflammation could equally promote beneficial lesion remodeling and repair. Distinct subpopulations of monocytes/macrophages (MOs/MPs) may critically determine the outcome of lesion-associated inflammation. Methods: We addressed the role of bone marrow-derived MOs/MPs in 2 different mouse models of ischemic stroke using a combined cell-specific depletion, chemokine receptor knockout, bone marrow chimeric, and pharmacological approach. Results: Starting within 24 hours of stroke onset, immature Ly6chi monocytes infiltrated into the infarct border zone and differentiated into mature Ly6clo phagocytes within the lesion compartment. MO/MP infiltration was CCR2-dependent, whereas we did not obtain evidence for additional recruitment via CX3CR1. Depletion of circulating MOs/MPs or selective targeting of CCR2 in bone marrow-derived cells caused delayed clinical deterioration and hemorrhagic conversion of the infarctions. Bleeding frequently occurred around thin-walled, dilated neovessels in the infarct border zone and was accompanied by decreased expression of transforming growth factor (TGF)-β1 and collagen-4, along with diminished activation of Smad2. Injection of TGF-β1 into the lesion border zone greatly reduced infarct bleeding in MO/MP-depleted mice. Interpretation: Bone marrow-derived MOs/MPs recruited via CCR2 and acting via TGF-β1 are essential for maintaining integrity of the neurovascular unit following brain ischemia. Future therapies should be aimed at enhancing physiological repair functions of CCR2+ MOs/MPs rather than blocking their hematogenous recruitment. ANN NEUROL 2012;71:743–752
Databáze: OpenAIRE
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