A mouse GM-CSF receptor antibody attenuates neutrophilia in mice exposed to cigarette smoke

Botelho, Fernando Mendes; Nikota, Jake K.; Bauer, Carla M. T.; Davis, Neil; Cohen, E. Suzanne; Anderson, Ian K.; Coyle, Anthony J.; Kolbeck, Roland; Humbles, Alison A.; Stämpfli, Martin R.; Sleeman, Matthew A.

doi:10.1183/09031936.00076210

Cited by 23 publications

(30 citation statements)

References 40 publications

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“…Despite the accumulation of phospholipids, we observed no difference in the recruitment of immune cells in anti-GM-CSF-treated animals. This observation is in contrast to previous reports, showing that GM-CSF blockade attenuated inflammatory processes [17,23]. This is probably a consequence of the dose of antibody used in the current study, which was substantially lower than that previously used to inhibit inflammatory processes.…”

Section: Figurecontrasting

confidence: 55%

“…This is probably a consequence of the dose of antibody used in the current study, which was substantially lower than that previously used to inhibit inflammatory processes. This suggests that, in addition to the previously documented role in neutrophil recruitment [17,23], GM-CSF activates mechanisms involved in the processing of damaged lipids following smoke exposure.…”

Section: Figurementioning

confidence: 94%

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Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice

et al. 2015

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Overwhelming evidence links inflammation to the pathogenesis of smoking-related pulmonary diseases, especially chronic obstructive pulmonary disease (COPD). Despite an increased understanding of the disease pathogenesis, mechanisms initiating smoking-induced inflammatory processes remain incompletely understood.To investigate the mechanisms that initiate and propagate smoke-induced inflammation, we used a wellcharacterised mouse model of cigarette smoke exposure, mice deficient for interleukin (IL)-1α, IL-1β and Toll-like receptor 4, and antibodies blocking granulocyte-macrophage colony-stimulating factor (GM-CSF). Studies were also pursued using intranasal delivery of human oxidised low-density lipoprotein (hOxLDL), a source of oxidised lipids, to investigate the inflammatory processes associated with impaired lipid homeostasis.We found that cigarette smoke exposure rapidly led to lipid accumulation in pulmonary macrophages, a defining feature of foam cells, which in turn released high levels of IL-1α. In smoke-exposed IL-1α-deficient mice, phospholipids accumulated in the bronchoalveolar lavage, a phenomenon also observed when blocking GM-CSF. Intranasal administration of hOxLDL led to lipid accumulation in macrophages and initiated an inflammatory process that mirrored the characteristics of cigarette smoke-induced inflammation.These findings identify a link between lipid accumulation in macrophages, inflammation and damaged surfactant, suggesting that the response to damaged pulmonary surfactant is a central mechanism that drives cigarette smoke-induced inflammation. Further investigations are required to explore the role of distorted lipid homeostasis in the pathogenesis of COPD. @ERSpublications Lipid accumulation in pulmonary macrophages drives cigarette smoke-induced lung inflammation

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Section: Figurecontrasting

confidence: 55%

Section: Figurementioning

confidence: 94%

Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice

et al. 2015

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“…In experimental animals, exposure to cigarette smoke consistently upregulates MMP-12 production and release [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]; this phenomenon appears to be much more frequent than upregulation of any other MMP, although we make that statement with caution because MMP-12 has been examined much more frequently than other MMPs.…”

Section: Mmps In Emphysema: Mmp-12mentioning

confidence: 67%

“…BOTELHO et al [10] showed that smoke upregulated production of granulocyte macrophage colony-stimulating factor (GM-CSF) in mice and that an antibody to GM-CSF or its receptor prevented smoke-mediated increases in MMP-12 release, while at the same time decreasing neutrophil and dendritic cell influx. Similar results using anti-GM-CSF antibodies were reported by VLAHOS et al [18], who also noted that antibody treatment decreased production of TNF-a and the chemokine MIP-2, without decreasing MMP-9 production.…”

Section: Mmps In Emphysema: Mmp-12mentioning

confidence: 99%

Matrix metalloproteinases in COPD

Churg

Zhou²,

Wright³

2011

Eur Respir J

240

116

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There is considerable evidence that matrix metalloproteinases (MMPs) are up-and/or downregulated in chronic obstructive pulmonary disease (COPD), particularly in emphysema, in which they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD. In cigarette smoke-induced animal models of emphysema, MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs, evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodelling, smokeinduced pulmonary hypertension and chronic bronchitis, but MMP-12 participates in experimental small airway modelling. To date, the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodelling, but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.

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“…MMPs have shown to be critically involved in all these processes [16,17], and in particular phenotypes presenting with the overlap of asthma and COPD are associated with risk alleles of variant MMP genes with differences in the expression of their gene products [18,19].…”

mentioning

confidence: 99%

MMPs are regulatory enzymes in pathways of inflammatory disorders, tissue injury, malignancies and remodelling of the lung

Müller–Quernheim¹

2011

Eur Respir J

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A mouse GM-CSF receptor antibody attenuates neutrophilia in mice exposed to cigarette smoke

Cited by 23 publications

References 40 publications

Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice

Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice

Matrix metalloproteinases in COPD

MMPs are regulatory enzymes in pathways of inflammatory disorders, tissue injury, malignancies and remodelling of the lung

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