Ibeas Elvira, Fuentes Lucía, Martín Rubén, Hernández Marita, Nieto Maria Luisa
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas/Universidad de Valladolid, C/ Sanz y Fores s/n., 47005 Valladolid, Spain.
Cardiovasc Res. 2009 Jan 1;81(1):54-63. doi: 10.1093/cvr/cvn234. Epub 2008 Aug 28.
Human atherosclerotic plaques express markers of macrophage/dendritic cells as well as high levels of inflammatory proteins such as secreted phospholipase A(2) type IIA (sPLA(2)-IIA). To understand the cellular changes associated with the progress of atherosclerosis, we evaluated the role of sPLA(2)-IIA in mediating monocyte recruitment and differentiation into antigen-presenting cells.
The effect of sPLA(2)-IIA on monocyte differentiation was evaluated in human THP-1 cells, a cellular line widely used as a model for monocyte-macrophage differentiation. Changes in functional processes, morphology and expression of antigens, characteristic of differentiated cells, were monitored over a 1-3 day period. sPLA(2)-IIA inhibited CD14 expression in a time- and concentration-dependent manner and upregulated dendritic cell-specific ICAM-3 grabbing non-integrin levels at the cell surface, findings that were the same for human monocytes. In addition, sPLA(2)-IIA-differentiated cells showed a dendritic cell phenotype characterized by the generation of fine dendritic protrusions and an increase in surface markers such as CD40, CD83, CD54, CD61, and CD62L. Furthermore, cell adhesion, migration, endocytic activity, and allogeneic T cell proliferation capacity were markedly increased after sPLA(2)-IIA treatment.
sPLA(2)-IIA induces the differentiation of mononuclear cells and increases their adhesive and migratory capabilities, which suggests a novel function for sPLA(2)-IIA as a mediator connecting innate and adaptive immunity. These findings may provide insight into the immuno-inflammatory processes occurring in atherosclerosis, helping us to understand the cellular changes associated with the development of atherosclerosis.
人类动脉粥样硬化斑块表达巨噬细胞/树突状细胞标志物以及高水平的炎症蛋白，如分泌型磷脂酶A2-IIA（sPLA(2)-IIA）。为了解与动脉粥样硬化进展相关的细胞变化，我们评估了sPLA(2)-IIA在介导单核细胞募集和分化为抗原呈递细胞中的作用。
在人THP-1细胞中评估sPLA(2)-IIA对单核细胞分化的影响，THP-1细胞系广泛用作单核细胞-巨噬细胞分化的模型。在1-3天的时间内监测分化细胞特有的功能过程、形态和抗原表达的变化。sPLA(2)-IIA以时间和浓度依赖性方式抑制CD14表达，并上调细胞表面树突状细胞特异性ICAM-3结合非整合素水平，这一结果在人类单核细胞中也是相同的。此外，经sPLA(2)-IIA分化的细胞呈现树突状细胞表型，其特征是产生细小的树突状突起以及表面标志物如CD40、CD83、CD54、CD61和CD62L增加。此外，sPLA(2)-IIA处理后细胞黏附、迁移、内吞活性和异体T细胞增殖能力显著增强。
sPLA(2)-IIA诱导单核细胞分化并增强其黏附和迁移能力，这表明sPLA(2)-IIA作为连接固有免疫和适应性免疫的介质具有新功能。这些发现可能有助于深入了解动脉粥样硬化中发生的免疫炎症过程，帮助我们理解与动脉粥样硬化发展相关的细胞变化。
