Abstract TP257: Apoptotic Erythrocytes Attenuate Macrophages Proinflammatory Phenotype in Intracerebral Hemorrhage
Stroke(2016)
Abstract
Introduction: Inflammation contributes to both injury and recovery after intracerebral hemorrhage (ICH). Our previous studies showed that blood-derived CCR2 + monocytes/macrophages infiltration induces brain injury in acute ICH, whereas these cells are also essential for hematoma clearance at later stage of ICH. However, the mechanism that educates macrophages (MΦ) to change from classical activation to assisting in recovery in the hemorrhagic brain is still missing. In wound healing, contact with apoptotic cells induces macrophage alternative activation. Hypothesis: Apoptotic erythrocytes activate phosphatidylserine (PtdSer) receptors on MΦ to decrease MΦ proinflammatory response and induce MΦ alternative activation to aid in hematoma clearance. Methods: Bone marrow-derived macrophages were treated with thrombin to induce MΦ proinflammatory activation and to mimic ICH in vitro . We used PHK-26 labeled-apoptotic erythrocytes and recombinant annexin V to competitively inhibit PtdSer-receptor interactions to study the effect of apoptotic erythrocytes on MΦ phenotype and erythrophagocytosis ability. RT-qPCR and immunofluorescence were performed to detect MΦ polarization genes expression and the engulfment of erythrocytes. Results: Exposure to apoptotic erythrocytes decreased proinflammatory genes TNF-alpha (∼50%) and CD86 (∼30%) up-regulation induced by thrombin (10 U/ml) treatment for 12 hour (Figure). Recombinant annexin V (10μg) abolishes the benefit from apoptotic erythrocytes and reduces MΦ erythrophagocytosis. Conclusions: Macrophage alternative activation and erythrophagocytosis is induced by exposure to apoptotic erythrocytes in a PtdSer-dependent manner. Targeting PtdSer sensing receptor on MΦ could be a potential therapeutic strategy to promote MΦ alternative activation and subsequently to enhance hematoma clearance in ICH.
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Key words
Intracerebral hemorrhage,Immunology,Blood cells,Receptors,Stroke recovery
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