Serum from patients with systemic vasculitis induces alternatively activated macrophage M2c polarization

Ohlsson, Susanne; Linge, Petrus; Gullstrand, Birgitta; Lood, Christian; Johansson, Ann-Katrin; Ohlsson, Sophie; Lundqvist, Andrea; Bengtsson, Anders; Carlsson, Fredric; Hellmark, Thomas

doi:10.1016/j.clim.2014.02.016

Cited by 47 publications

(43 citation statements)

References 32 publications

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“…This unexpected finding may be due to the ongoing Th2 response of patients with GPA evaluated in this study, reflected by the frequent lymphoid follicles observed in parallel with granulomatous airway inflammation and by the high frequency (94.3%) of a positive ANCA test, indicating a shift towards a Th2 response [18]. Indeed, it is worth mentioning that sera from patients with AAV had a tendency to shift towards an M2c phenotype in macrophages regardless of disease activity, whereas sera from health controls led to an M0 phenotype [19]. Alternatively, another mechanism to explain the predominant M2 phenotype in GPA is the influence of therapy on our results; M2c macrophages may be induced by exposure to glucocorticoids [20].…”

Section: Discussionmentioning

confidence: 99%

M2 macrophage is the predominant phenotype in airways inflammatory lesions in patients with granulomatosis with polyangiitis

et al. 2017

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BackgroundMacrophages may present two distinct phenotypes indicated as M1 and M2 under different stimuli. M1 and M2 macrophages have divergent functions that range from enhancement of inflammation for M1 to tissue repair and remodeling for M2 macrophages. The objective of this study was to evaluate the distribution of M1 and M2 macrophage phenotypes in biopsies from the airways of patients with active granulomatosis with polyangiitis (GPA) and to analyze their associations with T and B cells in those biopsies, and with nasal carriage of Staphylococcus aureus, disease parameters and therapy.MethodsConsecutive GPA patients (n = 35) with active airway disease, who underwent respiratory tract biopsy were included. Immunohistochemical evaluation was performed to assess the distribution of macrophages and T and B cells using the markers CD68, CD3 and CD20, respectively. CD86 was used as the M1 marker and CD163 as the M2 marker while Tbet and GATA-3 were used as Th1 and Th2 markers, respectively. At the time of the biopsy patients were assessed for nasal carriage of Staphylococcus aureus and treatment.ResultsPercentages of macrophages and T cells were significantly higher than those of B cells in lesional tissue from the respiratory tract in GPA. M2 macrophages and Th2 cells were more frequent than M1 macrophages (p = 0.0007) and Th1 cells (p < 0.0001), respectively. Percentages of T cells were higher in nose biopsies than in biopsies from other sites (p = 0.021); macrophages and CD163+ macrophages were more predominant in biopsy sites other than the nose (p = 0.039 and p = 0.012, respectively). Carriage of Staphylococcus aureus was associated with higher T cell scores (p = 0.014). The frequency of macrophages, especially M2 macrophages, was higher in GPA patients treated with immunosuppressive agents (p = 0.010); daily prednisolone dose was positively correlated with all macrophage markers. However, in multivariate analysis no independent associations were found between disease parameters and therapy with macrophage markers or T cells.ConclusionIn GPA, M2 is the predominant macrophage phenotype in the respiratory tract. Although some associations were observed between macrophages and T cells with therapy and nasal carriage of Staphylococcus aureus, they were not independently significant in multivariate analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1310-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

M2 macrophage is the predominant phenotype in airways inflammatory lesions in patients with granulomatosis with polyangiitis

et al. 2017

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“…Although it can be produced by many other cell types such as neutrophils, lymphocytes, NK cells, and mast cells, TNF‐α is chiefly produced by activated macrophages . In activated macrophages, M1 and M2b are the main cell types expressing and secreting TNF‐α . Accumulating evidences have shown that TNF‐α, in combination with other markers, such as IL‐10, LIGHT, CCL1, or/and IL‐6, can discriminate M2b from the other subtypes of macrophages very well .…”

Section: Phenotypic Markers Of M2bmentioning

confidence: 99%

“…In activated macrophages, M1 and M2b are the main cell types expressing and secreting TNF‐α . Accumulating evidences have shown that TNF‐α, in combination with other markers, such as IL‐10, LIGHT, CCL1, or/and IL‐6, can discriminate M2b from the other subtypes of macrophages very well . In addition, TNF‐α is considered a marker of M2b macrophages in many review articles …”

Section: Phenotypic Markers Of M2bmentioning

confidence: 99%

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M2b macrophage polarization and its roles in diseases

Wang

Zhang

et al. 2018

Journal of Leukocyte Biology

588

455

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Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages. Macrophages commonly exist in two distinct subsets: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2b, a subtype of M2 macrophages, has attracted increasing attention over the past decade due to its strong immune‐regulated and anti‐inflammatory effects. A wide variety of stimuli and multiple factors modulate M2b macrophage polarization in vitro and in vivo. M2b macrophages possess both protective and pathogenic roles in various diseases. Understanding the mechanisms of M2b macrophage activation and the modulation of their polarization might provide a great perspective for the design of novel therapeutic strategies. The purpose of this review is to discuss current knowledge of M2b macrophage polarization, the roles of M2b macrophages in a variety of diseases and the stimuli to modulate M2b macrophage polarization.

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“…Ohlsson et al have reported that serum from AAV patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) induces a macrophage subtype mainly resembling M2c (60). The relevance of this finding is difficult to assess as insufficient data are available to which extent macrophages in AAV patients are biased towards any of the functional subspecializations.…”

Section: Macrophage Polarizationmentioning

confidence: 99%

Macrophages in vascular inflammation – From atherosclerosis to vasculitis

et al. 2015

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The spectrum of vascular inflammatory disease ranges from atherosclerosis and hypertension, widespread conditions affecting large proportions of the population, to the vasculitides, rare syndromes leading to fast and irreversible organ failure. Atherosclerosis progresses over decades, inevitably proceeding through multiple phases of disease and causes its major complications when the vessel wall lesion ruptures, giving rise to lumen-occlusive atherothrombosis. Vasculitides of medium and large arteries progress rapidly, causing tissue ischemia through lumen-occlusive intimal hyperplasia. In both disease entities, macrophages play a decisive role in pathogenesis, but function in the context of other immune cells that direct their differentiation and their functional commitments. In atherosclerosis, macrophages are involved in the removal of lipids and tissue debris and make a critical contribution to tissue damage and wall remodeling. In several of the vasculitides, macrophages contribute to granuloma formation, a microstructural platform optimizing macrophage-T cell interactions, antigen containment and inflammatory amplification. By virtue of their versatility and plasticity, macrophages are able to promote a series of pathogenic functions, ranging from the release of cytokines and enzymes, the production of reactive oxygen species, presentation of antigen and secretion of tissue remodeling factors. However, as short-lived cells that lack memory, macrophages are also amendable to reprogramming, making them promising targets for anti-inflammatory interventions.

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Serum from patients with systemic vasculitis induces alternatively activated macrophage M2c polarization

Cited by 47 publications

References 32 publications

M2 macrophage is the predominant phenotype in airways inflammatory lesions in patients with granulomatosis with polyangiitis

M2 macrophage is the predominant phenotype in airways inflammatory lesions in patients with granulomatosis with polyangiitis

M2b macrophage polarization and its roles in diseases

Macrophages in vascular inflammation – From atherosclerosis to vasculitis

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