Elevated Levels of the Neutrophil Chemoattractant Pro–Platelet Basic Protein in Macrophages From Individuals With Chronic and Allergic Aspergillosis

Smith, Nicola L.; Bromley, Michael; Denning, David W.; Simpson, Angela; Bowyer, Paul

doi:10.1093/infdis/jiu490

Cited by 21 publications

(18 citation statements)

References 40 publications

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“…ORM1 appears to function in regulating the activity of the immune system during the acute-phase reaction and has been identified as an acute exacerbation of COPD-specific immunomodulatory mediator [62]. PPBP serves as a potent neutrophil chemoattractant and activator, and its elevated expression in the bronchial mucosa might be involved in the pathogenesis of COPD [63,64]. In addition, VCAM1 was shown to express in endothelial cells of atopic asthma cases, but not COPD cases [65], and present an association with lung function [66].…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in chronic obstructive pulmonary disease via bioinformatic analysis

Huang

Guo

et al. 2019

FEBS Open Bio

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Chronic obstructive pulmonary disease (COPD) is a multifactorial and heterogeneous disease that creates public health challenges worldwide. The underlying molecular mechanisms of COPD are not entirely clear. In this study, we aimed to identify the critical genes and potential molecular mechanisms of COPD by bioinformatic analysis. The gene expression profiles of lung tissues of COPD cases and healthy control subjects were obtained from the Gene Expression Omnibus. Differentially expressed genes were analyzed by integration with annotations from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, followed by construction of a protein‐protein interaction network and weighted gene coexpression analysis. We identified 139 differentially expressed genes associated with the progression of COPD, among which 14 Hub genes were identified and found to be enriched in certain categories, including immune and inflammatory response, response to lipopolysaccharide and receptor for advanced glycation end products binding; in addition, these Hub genes are involved in multiple signaling pathways, particularly hematopoietic cell lineage and cytokine‐cytokine receptor interaction. The 14 Hub genes were positively or negatively associated with COPD by wgcna analysis. The genes CX3CR1, PTGS2, FPR1, FPR2, S100A12, EGR1, CD163, S100A8 and S100A9 were identified to mediate inflammation and injury of the lung, and play critical roles in the pathogenesis of COPD. These findings improve our understanding of the underlying molecular mechanisms of COPD.

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Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in chronic obstructive pulmonary disease via bioinformatic analysis

Huang

Guo

et al. 2019

FEBS Open Bio

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“…Neutrophils and alveolar macrophages are important human innate cells against Aspergillus infection through phagocytosis and secretion of the neutrophil extracellular traps (NETs) [ 38 ]. An experimental study by Smith et al (2015) showed increased levels of macrophage-derived neutrophil chemoattractant pro-platelet basic proteins, which is thought to be pathological in ABPA and CCPA patients [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis

Bongomin

Harris²,

Foden³

et al. 2017

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We evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). Patients with complete medical and radiological records, white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six (4%) patients had lymphopenia in all five CD variables. There were 62 (43%) patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%) had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15 (10%) of whom had absolute CD4 counts <200/μL. Multivariable logistic regression showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR), 5.53; 95% Confidence Interval (CI), 1.43–21.33; p = 0.013), and emphysema (OR, 4.58; 95% CI; 1.36–15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27; 95% CI, 0.10–0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR, 2.95; 95% CI, 1.30–6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI, 1.39–17.57; p = 0.014). Several subtle immune defects are found in CPA.

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“…Using ShinyGO 20 and MetaScape 21 , we mapped proteins differentially abundant in at least 4/5 samples to known gene-ontology biological processes. Proteins more abundant in SLE NDNs relative to HC NDNs mapped to neutrophil activation networks, including proteins facilitating migration to inflammatory sites and release from bone marrow [22][23][24] . Some proteins associated with neutrophil activation were most abundant in SLE LDGs ( Figure 1E-F).…”

Section: The Ldg Proteome Displays a Distinct Profilementioning

confidence: 99%

Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus

et al. 2020

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ObjectivesLow-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE.MethodsProteomic/phosphoproteomic analyses were performed in healthy control (HC) normal density neutrophils (NDNs), SLE NDNs and autologous SLE LDGs. The biophysical properties of these neutrophil subsets were analysed by real-time deformability cytometry and lattice light-sheet microscopy. A two-dimensional endothelial flow system and a three-dimensional microfluidic microvasculature mimetic (MMM) were used to decouple the contributions of cell surface mediators and biophysical properties to neutrophil trafficking, respectively.ResultsProteomic and phosphoproteomic differences were detected between HC and SLE neutrophils and between SLE NDNs and LDGs. Increased abundance of type 1 interferon-regulated proteins and differential phosphorylation of proteins associated with cytoskeletal organisation were identified in SLE LDGs relative to SLE NDNs. The cell surface of SLE LDGs was rougher than in SLE and HC NDNs, suggesting membrane perturbances. While SLE LDGs did not display increased binding to endothelial cells in the two-dimensional assay, they were increasingly retained/trapped in the narrow channels of the lung MMM.ConclusionsModulation of the neutrophil proteome and distinct changes in biophysical properties are observed alongside differences in neutrophil trafficking. SLE LDGs may be increasingly retained in microvasculature networks, which has important pathogenic implications in the context of lupus organ damage and small vessel vasculopathy.

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Elevated Levels of the Neutrophil Chemoattractant Pro–Platelet Basic Protein in Macrophages From Individuals With Chronic and Allergic Aspergillosis

Abstract: The results suggest a role for increased PPBP expression in ABPA and CCPA. Repression of PPBP expression may benefit some patients. Increased PPBP expression in ABPA and CCPA may be useful as a future diagnostic tool or possible target for novel therapeutics.

Cited by 21 publications

References 40 publications

Identification of differentially expressed genes and signaling pathways in chronic obstructive pulmonary disease via bioinformatic analysis

Identification of differentially expressed genes and signaling pathways in chronic obstructive pulmonary disease via bioinformatic analysis

Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis

Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus

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