Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
J Immunol. 2010 Aug 15;185(4):2044-50. doi: 10.4049/jimmunol.1000017. Epub 2010 Jul 21.
Clearance of apoptotic exudate neutrophils (efferocytosis) induces either pro- or anti-inflammatory responses in mouse macrophages depending on host genetic background. In this study, we investigated whether neutrophil efferocytosis induces a stable macrophage phenotype that could be recalled by late restimulation with LPS. Bone marrow-derived macrophages previously stimulated by pro- but not anti-inflammatory neutrophil efferocytosis expressed a regulatory/M2b phenotype characterized by low IL-12 and high IL-10 production following restimulation, increased expression of LIGHT/TNF superfamily 14, Th2-biased T cell responses, and permissive replication of Leishmania major. Induction of regulatory/M2b macrophages required neutrophil elastase activity and was partially dependent on TLR4 signaling. These results suggested that macrophage differentiation to a regulatory phenotype plays a role in resolution of inflammation but could contribute to increased humoral Ab responses and parasite persistence in the infected host.
凋亡细胞外溢中性粒细胞（胞葬作用）的清除在取决于宿主遗传背景的情况下，会诱导小鼠巨噬细胞产生促炎或抗炎反应。在这项研究中，我们研究了中性粒细胞胞葬作用是否会诱导一种稳定的巨噬细胞表型，这种表型可以通过后期用 LPS 再次刺激来召回。先前受促炎而非抗炎性中性粒细胞胞葬作用刺激的骨髓来源的巨噬细胞表达一种调节性/M2b 表型，其特征是在再次刺激后产生低水平的 IL-12 和高水平的 IL-10，表达增加的 LIGHT/TNF 超家族成员 14，偏向 Th2 的 T 细胞反应，以及利什曼原虫的允许复制。调节性/M2b 巨噬细胞的诱导需要中性粒细胞弹性蛋白酶活性，并且部分依赖于 TLR4 信号。这些结果表明，巨噬细胞向调节性表型的分化在炎症消退中发挥作用，但可能导致感染宿主中体液 Ab 反应增加和寄生虫持续存在。
