Macrophage migration inhibitory factor, a role in COPD

Husebø, Gunnar Reksten; Bakke, Per; Grønseth, Rune; Hardie, Jon A.; Ueland, Thor; Aukrust, Pål; Eagan, Tomas Mikal

doi:10.1152/ajplung.00461.2015

Cited by 20 publications

(21 citation statements)

References 45 publications

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“…Lastly, CXCR4 is a chemokine receptor for pro-inflammatory mediators such as macrophage migration inhibitor factor (MIF), which is a pleiotropic cytokine that antagonizes both apoptosis and premature senescence [ 56 , 57 , 58 ]. It has been shown to be elevated and implicated in the pathogenesis of COPD [ 59 ]. Together, upregulation of these genes suggest that these non-polarized macrophages were also pro-inflammatory in nature and suppress inflammation resolution and tissue repair.…”

Section: Discussionmentioning

confidence: 99%

Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD)

et al. 2020

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Lung macrophages are the key immune effector cells in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Several studies have shown an increase in their numbers in bronchoalveolar lavage fluid (BAL) of subjects with COPD compared to controls, suggesting a pathogenic role in disease initiation and progression. Although reduced lung macrophage phagocytic ability has been previously shown in COPD, the relationship between lung macrophages’ phenotypic characteristics and functional properties in COPD is still unclear. (1) Methods: Macrophages harvested from bronchoalveolar lavage (BAL) fluid of subjects with and without COPD (GOLD grades, I–III) were immuno-phenotyped, and their function and gene expression profiles were assessed using targeted assays. (2) Results: BAL macrophages from 18 COPD and 10 (non-COPD) control subjects were evaluated. The majority of macrophages from COPD subjects were non-polarized (negative for both M1 and M2 markers; 77.9%) in contrast to controls (23.9%; p < 0.001). The percentages of these non-polarized macrophages strongly correlated with the severity of COPD (p = 0.006) and current smoking status (p = 0.008). Non-polarized macrophages demonstrated poor phagocytic function in both the control (p = 0.02) and COPD (p < 0.001) subjects. Non-polarized macrophages demonstrated impaired ability to phagocytose Staphylococcus aureus (p < 0.001). They also demonstrated reduced gene expression for CD163, CD40, CCL13 and C1QA&B, which are involved in pathogen recognition and processing and showed an increased gene expression for CXCR4, RAF1, amphiregulin and MAP3K5, which are all involved in promoting the inflammatory response. (3) Conclusions: COPD is associated with an abundance of non-polarized airway macrophages that is related to the severity of COPD. These non-polarized macrophages are predominantly responsible for the poor phagocytic capacity of lung macrophages in COPD, having reduced capacity for pathogen recognition and processing. This could be a key risk factor for COPD exacerbation and could contribute to disease progression.

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Section: Discussionmentioning

confidence: 99%

Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD)

et al. 2020

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“…A third study suggested that peripheral blood mononuclear gene expression of MIF inversely correlated with disease severity as measured by percent emphysema and spirometric evidence of airway obstruction (9). Finally, a recent study, and the largest of its kind, has shown that, although MIF was increased in moderate disease (GOLD II) compared with healthy never, current, and former smokers, there was a significant decrease in circulating MIF among patients with severe and very severe disease (GOLD III, IV) (61). Overall these studies suggest that although MIF may be increased among healthy smokers or smokers with moderate disease, circulating levels of MIF fall as the disease progresses.…”

Section: Mif In Animal Models and Human Studies Of Age-related Lung Dmentioning

confidence: 98%

Role of macrophage migration inhibitory factor in age-related lung disease

Sauler

Bucala

Lee

2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…[52]. Additionally, impairment of autophagy is also associated with an increase in ROS-dependent macrophage migration inhibitory factor (MIF) activity [57], which further promotes pro-inflammatory cytokine (such as IL-1β) production and release [54], as well as hyper-inflammatory response in COPD airways [58]. In addition, as a proof of concept, macrophages isolated from COPD subjects are defective in autophagy-mediated phagocytosis (xenophagy) resulting in impaired clearance of bacteria/viruses [59–61].…”

Section: Introductionmentioning

confidence: 99%

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology

Bodas

Vij

2017

Respir Res

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Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

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Macrophage migration inhibitory factor, a role in COPD

Cited by 20 publications

References 45 publications

Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD)

Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD)

Role of macrophage migration inhibitory factor in age-related lung disease

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology

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