Macrophages in Allergic Asthma: Fine-Tuning Their Pro- and Anti-Inflammatory Actions for Disease Resolution

Abstract

Macrophages exert prominent effects in the defense of the respiratory tract from airborne pathogens. These cells are specialized to recognize, phagocytose, and destroy these infectious agents and then promote appropriate tissue repair after successful pathogen clearance. For reasons that are not presently clear, macrophages appear to be inappropriately activated during asthma responses. Evidence stems from the appearance of either classically (or M1) and alternatively activated (or M2) cells in the alveolar compartment of asthmatic lung. Macrophages localized in the interstitial area of the lung appear to be less prone to polarization toward either the M1 or M2 phenotype as these cells predominately express interleukin-10 and exhibit immunoregulatory properties. Effective treatment of clinical asthma, regardless of severity, might depend on restoring an appropriate balance between M1, M2, and immunoregulatory macrophages in the lung.

GM‐CSF– and M‐CSF–primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures

“…Mf in the M2 spectrum confer fibrosis and remodeling (22,41), and another effect of Cys-LTs is induction of TGFb, furin, and VEGF, leading to tissue remodeling in chronic asthma (44)(45)(46). It is tempting to speculate that the M-CSF-derived Mfs studied here, with high capacity for LTC 4 biosynthesis, may resemble pulmonary M2 cells active in allergic lung inflammation (22).…”

“…A striking difference was that the M-CSF Mfs produced high amounts of LTC 4 . This is of considerable interest in relation to the role of Cys-LTs in T-helper 2-driven asthma, in which there is an enhanced presence of M2 Mfs (22,41). Cys-LTs are very potent inducers of vascular permeability in postcapillary venules, leading to exudates containing plasma proteins including the complement system, which can opsonize all bacteria and can lyse Gram-negative bacteria.…”

Alveolar Macrophages Are Critical for the Inhibition of Allergic Asthma by Mesenchymal Stromal Cells

“…Whereas M1 macrophages produce high levels of proinflammatory cytokines and express strong antimicrobial activity, M2 macrophages produce anti-inflammatory cytokines, such as IL-10, and exhibit efficient phagocytic activity. In the Th2-driven lung environment during asthma, IL-4 and IL-13 can contribute to priming and skewing of M2 macrophages (41). Although M2 macrophages can inhibit the production of proinflammatory molecules and are traditionally described as immunosuppressive, their role in allergic asthma remains controversial, as some studies have demonstrated a role for M2 macrophages in promoting allergic inflammation (41,42).…”

“…In the Th2-driven lung environment during asthma, IL-4 and IL-13 can contribute to priming and skewing of M2 macrophages (41). Although M2 macrophages can inhibit the production of proinflammatory molecules and are traditionally described as immunosuppressive, their role in allergic asthma remains controversial, as some studies have demonstrated a role for M2 macrophages in promoting allergic inflammation (41,42). Our data indicate that the interaction between MSCs and AMs in this setting is not be as straightforward as modulating M1/M2 polarization.…”

Macrophages and CSF-1

“…Indeed, immunological research shows that the M1/M2 balance is a two-edged sword and that both provide important functions in their appropriate context. 7 Dysregulation of M2 macrophages is also associated with enhanced matrix production and pathological implications observed in disorders such as in asthma 143 and the immunosuppressive functions of M2s and CSF-1 is linked to tumor growth and metastasis. 144,145 CSF-1 has also been linked to the formation of atherosclerotic plaques.…”