Abdelaziz Mohamed Hamed, Abdelwahab Sayed F, Wan Jie, Cai Wei, Huixuan Wang, Jianjun Cheng, Kumar Kesavan Dinesh, Vasudevan Aparna, Sadek Ahmed, Su Zhaoliang, Wang Shengjun, Xu Huaxi
Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, 61511, Egypt.
J Transl Med. 2020 Feb 5;18(1):58. doi: 10.1186/s12967-020-02251-w.
Macrophages are heterogenous phagocytic cells with an important role in the innate immunity. They are, also, significant contributors in the adaptive immune system. Macrophages are the most abundant immune cells in the lung during allergic asthma, which is the most common chronic respiratory disease of both adults and children. Macrophages activated by Th1 cells are known as M1 macrophages while those activated by IL-4 and IL-13 are called alternatively activated macrophages (AAM) or M2 cells. AAM are subdivided into four distinct subtypes (M2a, M2b, M2c and M2d), depending on the nature of inducing agent and the expressed markers. BODY: IL-4 is the major effector cytokine in both alternative activation of macrophages and pathogenesis of asthma. Thus, the role of M2a macrophages in asthma is a major concern. However, this is controversial. Therefore, further studies are required to improve our knowledge about the role of IL-4-induced macrophages in allergic asthma, through precisive elucidation of the roles of specific M2a proteins in the pathogenesis of asthma. In the current review, we try to illustrate the different functions of M2a macrophages (protective and pathogenic roles) in the pathogenesis of asthma, including explanation of how different M2a proteins and markers act during the pathogenesis of allergic asthma. These include surface markers, enzymes, secreted proteins, chemokines, cytokines, signal transduction proteins and transcription factors.
AAM is considered a double-edged sword in allergic asthma. Finally, we recommend further studies that focus on increased selective expression or suppression of protective and pathogenic M2a markers.
巨噬细胞是异质性吞噬细胞，在固有免疫中起重要作用。它们也是适应性免疫系统的重要贡献者。巨噬细胞是过敏性哮喘（成人和儿童中最常见的慢性呼吸道疾病）发作时肺中最丰富的免疫细胞。由Th1细胞激活的巨噬细胞称为M1巨噬细胞，而由IL-4和IL-13激活的巨噬细胞称为替代性激活巨噬细胞（AAM）或M2细胞。根据诱导剂的性质和表达的标志物，AAM可细分为四种不同的亚型（M2a、M2b、M2c和M2d）。
IL-4是巨噬细胞替代性激活和哮喘发病机制中的主要效应细胞因子。因此，M2a巨噬细胞在哮喘中的作用是一个主要关注点。然而，这存在争议。因此，需要进一步研究，通过精确阐明特定M2a蛋白在哮喘发病机制中的作用，来增进我们对IL-4诱导的巨噬细胞在过敏性哮喘中作用的了解。在本综述中，我们试图阐述M2a巨噬细胞在哮喘发病机制中的不同功能（保护作用和致病作用），包括解释不同的M2a蛋白和标志物在过敏性哮喘发病过程中是如何发挥作用的。这些包括表面标志物、酶、分泌蛋白、趋化因子、细胞因子、信号转导蛋白和转录因子。
AAM在过敏性哮喘中被认为是一把双刃剑。最后，我们建议进一步开展研究，重点关注增加保护性和致病性M2a标志物的选择性表达或抑制。
