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Macrophages are a heterogeneous population of myeloid cells with phenotype and function modulated according to the microenvironment in which they are found. The lung resident macrophages known as Alveolar Macrophages (AM) and Interstitial Macrophages (IM) are localized in two different compartments. During lung homeostasis, macrophages can remove inhaled particulates, cellular debris and contribute to some metabolic processes. Macrophages may assume a pro-inflammatory phenotype after being classically activated (M1) or anti-inflammatory when being alternatively activated (M2). M1 and M2 have different transcription profiles and act by eliminating bacteria, viruses and fungi from the host or repairing the damage triggered by inflammation, respectively. Nevertheless, macrophages also may contribute to lung damage during persistent inflammation or continuous exposure to antigens. In this review, we discuss the origin and function of pulmonary macrophages in the context of homeostasis, infectious and non-infectious lung diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The resolution of inflammation is a dynamic process, characterized by the biosynthesis of pro-resolving mediators, including the lipid Lipoxin A4 (LXA 4 ). LXA 4 acts on the N-formyl peptide receptor 2 (FPR2/ALX) to mediate anti-inflammatory and pro-resolving effects. In order to exploit the therapeutic potential of endogenous LXA 4 in the context of inflammation we have recently developed synthetic LXA 4 mimetics (sLXms) including a dimethyl-imidazole-containing FPR2/ALX agonist designated AT-01-KG. Here, we have investigated the effect of treatment with AT-01-KG in established models of articular inflammation. In a model of gout, mice were injected with MSU crystals and treated with AT-01-KG at the peak of inflammatory response. The treatment decreased the number of neutrophils in the knee exudate, an effect which was accompanied by low levels of myeloperoxidase, CXCL1 and IL-1β in periarticular tissue. AT-01-KG treatment led to reduced tissue damage and hypernociception. The effects of AT-01-KG on neutrophil accumulation were not observed in MSU treated FPR2/3 -/- mice. Importantly, AT-01-KG induced resolution of articular inflammation by increasing neutrophil apoptosis and subsequent efficient efferocytosis. In a model of antigen-induced arthritis, AT-01-KG treatment also attenuated inflammatory responses. These data suggest that AT-01-KG may be a potential new therapy for neutrophilic inflammation of the joints., (Copyright © 2021 Elsevier Ltd. All rights reserved.)