Alternatively activated macrophages; a double-edged sword in allergic asthma

Abstract

Background: 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.

Conclusions: 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.

Keywords: Allergy; Asthma; Human/mice; IL-4; Lung; Macrophages.

Fig. 1

Protective and pathogenic proteins of human and murine M2a macrophages in allergic asthma. The protective proteins are the same in human and mice, representing in MRC1 that mediate allergen clearance, and IL-1RA that suppresses eosinophilic inflammation, Th2 activation and AHR, which induced by IL-1. The pathogenic proteins of human and mice are shared in three markers, TGM2 that induces eosinophilic inflammation, CCL17 and CCL22 that induces Th2 mediated allergic inflammation, and TGF β1 that induce airway remodeling. Murine M2a macrophages have another three unique pathogenic proteins, Arg1 that stimulate bronchoconstriction and airway remodeling, FIZZ1 that induces airway remodeling and finally CHI3L3 that also induces Airway remodeling and eosinophilic inflammation