Interleukin-1 beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice
Interleukin-1 beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice
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DOI：
10.1186/1742-2094-5-46
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发表时间：
2008-10-23
影响因子：
9.3
通讯作者：
Finsen, Bente
中科院分区：
文献类型：
--
作者：
Clausen, Bettina H.;Lambertsen, Kate L.;Finsen, Bente
背景：缺血性卒中后小胶质细胞和浸润性巨噬细胞表达白细胞介素-1 β (IL-1 β)和肿瘤坏死因子- α (tnf - α)。IL-1 β在缺血性卒中中主要具有神经毒性，而tnf - α可能具有神经毒性和/或神经保护作用。我们研究了小鼠缺血性卒中后IL-1 β和tnf - α是否通过重叠或分离的细胞群合成。方法：采用流式细胞术和免疫组织化学检测小鼠永久性大脑中动脉闭塞后6、12和24小时细胞中IL-1 β和tnf - α的共表达，并通过骨髓嵌合小鼠验证结果。结果：我们发现IL-1 β和tnf - α在大量分离的CD11b(+)CD45（低）小胶质细胞和CD11b(+)CD45（高）巨噬细胞中表达，细胞表达这两种细胞因子的情况很少。产生IL-1 β或tnf - α的Gr1（+）粒细胞数量非常低，我们没有观察到表达IL-1 β或tnf - α的T细胞或星形胶质细胞。结论：综上所述，小鼠缺血性脑卒中后，大量分离的小胶质细胞和巨噬细胞产生IL-1 β和tnf - α。我们的发现为小胶质细胞和巨噬细胞不同亚群之间的功能多样性提供了证据，这可能与未来中风抗炎疗法的设计有关。
Background: Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1 beta is primarily neurotoxic in ischemic stroke, TNF-alpha may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1 beta and TNF-alpha are synthesized by overlapping or segregated populations of cells after ischemic stroke in mice.Methods: We used flow cytometry and immunohistochemistry to examine cellular co-expression of IL-1 beta and TNF-alpha at 6, 12 and 24 hours after permanent middle cerebral artery occlusion in mice, validating the results by the use of bone marrow chimeric mice.Results: We found that IL-1 beta and TNF-alpha were expressed in largely segregated populations of CD11b(+)CD45(dim) microglia and CD11b(+)CD45(high) macrophages, with cells expressing both cytokines only rarely. The number of Gr1(+) granulocytes producing IL-1 beta or TNF-alpha was very low, and we observed no IL-1 beta- or TNF-alpha-expressing T cells or astrocytes.Conclusion: Taken together, the results show that IL-1 beta and TNF-alpha are produced by largely segregated populations of microglia and macrophages after ischemic stroke in mice. Our findings provide evidence of a functional diversity among different subsets of microglia and macrophages that is potentially relevant to future design of anti-inflammatory therapies in stroke.