Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR China.
Department of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, PR China.
Exp Cell Res. 2020 Jan 1;386(1):111708. doi: 10.1016/j.yexcr.2019.111708. Epub 2019 Nov 1.
Recent studies revealed that macrophages are polarized towards the M2 phenotype in an ovalbumin (OVA)-induced asthmatic model. Alveolar macrophages (AMs) are immune barriers in alveoli to various pathogens in the respiratory tract; AMs suppress Th2 cell proliferation, inhibit interleukin (IL)-4, IL-5, and IL-13 secretion, and protect against airway hyperresponsiveness in allergic asthma. However, the polarization status and effects of different types of AMs in the pathogenesis of asthma are not known. ATP/P2X7r, expressed mainly on macrophages and dendritic cells, is associated with acute and chronic asthmatic airway inflammation and Th2 immune responses in mice and humans and functions by activating the NLRP3 inflammasome complex and inducing proinflammatory cytokine release (IL-1β and IL-18). Therefore, we evaluated the association between the ATP/P2X7r axis and different types of AMs in the pathology of allergic asthma. A murine AM-depleted asthma model was established by administration of clodronate-encapsulated liposomes, and M1-or M2-AMs were adoptively transferred to confirm the effects of different AMs in allergic asthma. Brilliant Blue G and BzATP were administered to OVA/HDM-induced mice in vivo. Lipopolysaccharide + OVA, ATP, Brilliant Blue G, and BzATP were used to stimulate AMs isolated from control and asthmatic mice. We found that selective depletion of AMs aggravated lung inflammation in asthmatic mice. Further, M2-type AMs may play a key role in mediating asthmatic inflammatory responses via the adoptive transfer of M2-type AMs to AM-depleted asthmatic mice, and the phenotype of AMs differentiated to M2 type in asthma. P2X7r expression in M2-type AMs was higher than that in M1-type AMs. Activating P2X7r induced polarization of M2-type AMs and inhibited polarization of M1-type AMs, while blockage of P2X7r had the opposite effect. The ATP/P2X7r axis may participate in the pathogenesis of asthma by mediating the M2-type AM polarization.
最近的研究表明，在卵清蛋白（OVA）诱导的哮喘模型中，巨噬细胞向 M2 表型极化。肺泡巨噬细胞（AMs）是呼吸道中各种病原体进入肺泡的免疫屏障；AMs 抑制 Th2 细胞增殖，抑制白细胞介素（IL）-4、IL-5 和 IL-13 的分泌，并防止过敏性哮喘的气道高反应性。然而，不同类型的 AMs 在哮喘发病机制中的极化状态和作用尚不清楚。ATP/P2X7r 主要表达于巨噬细胞和树突状细胞上，与小鼠和人类的急性和慢性哮喘气道炎症和 Th2 免疫反应有关，并通过激活 NLRP3 炎性小体复合物和诱导促炎细胞因子释放（IL-1β 和 IL-18）发挥作用。因此，我们评估了 ATP/P2X7r 轴与过敏性哮喘中不同类型 AMs 的关系。通过给予包裹氯膦酸盐的脂质体来建立 AM 耗竭的哮喘模型，并采用过继转移 M1 或 M2-AMs 来确认不同 AMs 在过敏性哮喘中的作用。体内给予亮蓝 G 和 BzATP 给 OVA/HDM 诱导的小鼠。用脂多糖+OVA、ATP、亮蓝 G 和 BzATP 刺激来自对照和哮喘小鼠的 AMs。我们发现，AM 选择性耗竭加重哮喘小鼠的肺部炎症。此外，通过将 M2 型 AMs 过继转移至 AM 耗竭的哮喘小鼠，M2 型 AMs 可能在介导哮喘炎症反应中发挥关键作用，并且哮喘中 AMs 向 M2 型分化。M2 型 AMs 中的 P2X7r 表达高于 M1 型 AMs。激活 P2X7r 诱导 M2 型 AMs 极化，并抑制 M1 型 AMs 极化，而阻断 P2X7r 则产生相反的效果。ATP/P2X7r 轴可能通过介导 M2 型 AM 极化参与哮喘的发病机制。
