IL-33 and Superantigenic Activation of Human Lung Mast Cells Induce the Release of Angiogenic and Lymphangiogenic Factors

Cristinziano, Leonardo; Poto, Remo; Criscuolo, Gjada; Ferrara, Anne Lise; Galdiero, Maria Rosaria; Modestino, Luca; Loffredo, Stefania; Paulis, Amato de; Marone, Gianni; Spadaro, Giuseppe; Varricchi, Gilda

doi:10.3390/cells10010145

Cited by 42 publications

(42 citation statements)

References 160 publications

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“…Angiogenesis, the formation of new blood vessels, is a complex process modulated by a plethora of stimulatory and inhibitory factors [85,86]. There is some evidence the angiogenic switch in asthmatic airways involves the production of direct (e.g., VEGFs, angiopoietins) and indirect angiogenic factors (e.g., MMP-9, cysteinyl leukotrienes) [86,114,115]. Interestingly, the plasma concentrations of VEGF-A, which is also released by activated human PMNs [88,89], were similar in asthmatic and controls.…”

Section: Discussionmentioning

confidence: 99%

“…GM-CSF is considered a key orchestrator of neutrophil involvement in chronic airway inflammation [83,84]. VEGF-A, the most important angiogenic factor [85][86][87], is produced by activated human neutrophils [66,88,89]. Figure 4 shows that the plasma levels of MPO, MMP-9 and CXCL8 were significantly increased in asthmatics compared to healthy donors.…”

Section: Plasma Levels Of Neutrophil-derived Mediatorsmentioning

confidence: 99%

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Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

et al. 2021

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Neutrophils (PMNs) contain and release a powerful arsenal of mediators, including several granular enzymes, reactive oxygen species (ROS) and neutrophil extracellular traps (NETs). Although airway neutrophilia is associated with severity, poor response to glucocorticoids and exacerbations, the pathophysiological role of neutrophils in asthma remains poorly understood. Twenty-four patients with asthma and 22 healthy controls (HCs) were prospectively recruited. Highly purified peripheral blood neutrophils (> 99%) were evaluated for ROS production and activation status upon stimulation with lipopolysaccharide (LPS), N-formylmethionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). Plasma levels of myeloperoxidase (MPO), CXCL8, matrix metalloproteinase-9 (MMP-9), granulocyte–monocyte colony-stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF-A) were measured by ELISA. Plasma concentrations of citrullinated histone H3 (CitH3) and circulating free DNA (dsDNA) were evaluated as NET biomarkers. Activated PMNs from asthmatics displayed reduced ROS production and activation status compared to HCs. Plasma levels of MPO, MMP-9 and CXCL8 were increased in asthmatics compared to HCs. CitH3 and dsDNA plasma levels were increased in asthmatics compared to controls and the CitH3 concentrations were inversely correlated to the % decrease in FEV1/FVC in asthmatics. These findings indicate that neutrophils and their mediators could have an active role in asthma pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Section: Plasma Levels Of Neutrophil-derived Mediatorsmentioning

confidence: 99%

Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

et al. 2021

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“…The production of TSLP by HLMs suggested to us possible autocrine effects on these cells which are the most representative immune cells in human lung parenchyma [71,107]. We found that HLMs incubated with TSLP released significant amount of proinflammatory TNF-α and of several angiogenic (i.e., VEGF-A and ANGPT2) [108,109] and lymphangiogenic molecules (i.e., VEGF-C) [110,111]. These findings were supported by the observation that TSLP markedly increased the expression of TNF-α, VEGF-C, ANGPT2 mRNAs.…”

Section: Discussionmentioning

confidence: 69%

“…All the previously mentioned mediators play pivotal roles in tumor initiation and progression, tumor angiogenesis, and the formation of metastasis [109,112]. These results prompted us to investigate the expression of TSLP system in human lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Human Lung-Resident Macrophages Express and Are Targets of Thymic Stromal Lymphopoietin in the Tumor Microenvironment

Braile

Fiorelli

Sorriento

et al. 2021

Cells

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Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine highly expressed by epithelial cells and several innate and adaptive immune cells. TSLP exerts its biological effects by binding to a heterodimeric complex composed of TSLP receptor (TSLPR) and IL-7Rα. In humans, there are two TSLP isoforms: the short form (sfTSLP), constitutively expressed, and the long form (lfTSLP), which is upregulated in inflammation. TSLP has been implicated in the induction and progression of several experimental and human cancers. Primary human lung macrophages (HLMs), monocyte-derived macrophages (MDMs), and peripheral blood monocytes consitutively expressed sfTSLP mRNA. Incubation of HLMs, MDMs, and monocytes with lipopolysaccharide (LPS) or IL-4, but not with IL-13, induced TSLP release from HLMs. LPS, but not IL-4 or IL-13, induced CXCL8 release from HLMs. LPS, IL-4 alone or in combination with IL-13, induced the expression of lfTSLP, but not of sfTSLP from HLMs. Preincubation of HLMs with IL-4, alone or in combination with IL-13, but not IL-13 alone, synergistically enhanced TSLP release from LPS-activated macrophages. By contrast, IL-4, alone or in combination with IL-13, inhibited LPS-induced CXCL8 release from HLMs. Immunoreactive TSLP was detected in lysates of HLMs, MDMs, and monocytes. Incubation of HLMs with TSLP induced the release of proinflammatory (TNF-α), angiogenic (VEGF-A, angiopoietin 2), and lymphangiogenic (VEGF-C) factors. TSLP, TSLPR, and IL-7Rα were expressed in intratumoral and peritumoral areas of human lung cancer. sfTSLP and lfTSLP mRNAs were differentially expressed in peritumoral and intratumoral lung cancer tissues. The TSLP system, expressed in HLMs, MDMs, and monocytes, could play a role in chronic inflammatory disorders including lung cancer.

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“…Several other immune cells (e.g., macrophages, mast cells, neutrophils, ILC3, T H 1 cells, plasma cells) are sentinels in the mucosal system ( 79 ). Neutrophils exert anti-bacterial effects through the release of their stored and newly synthesized mediators and the formation of neutrophils extracellular traps NETs ( 80 ). T H 17 cells produce IL-22 that promotes secretion of anti-microbial peptides such as β-defensins by epithelial cells.…”

Section: Gut Microbiota In Cvidmentioning

confidence: 99%

Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions

et al. 2021

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Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority of CVID patients have polygenic inheritance. Immune dysfunction in CVID can frequently involve the gastrointestinal tract and lung. Few studies have started to investigate the gut microbiota profile in CVID patients. Overall, the results suggest that in CVID patients there is a reduction of alpha and beta diversity compared to controls. In addition, these patients can exhibit increased plasma levels of lipopolysaccharide (LPS) and markers (sCD14 and sCD25) of systemic immune cell activation. CVID patients with enteropathy exhibit decreased IgA expression in duodenal tissue. Mouse models for CVID unsatisfactorily recapitulate the polygenic causes of human CVID. The molecular pathways by which gut microbiota contribute to systemic inflammation and possibly tumorigenesis in CVID patients remain poorly understood. Several fundamental questions concerning the relationships between gut microbiota and the development of chronic inflammatory conditions, autoimmune disorders or cancer in CVID patients remain unanswered. Moreover, it is unknown whether it is possible to modify the microbiome and the outcome of CVID patients through specific therapeutic interventions.

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IL-33 and Superantigenic Activation of Human Lung Mast Cells Induce the Release of Angiogenic and Lymphangiogenic Factors

Cited by 42 publications

References 160 publications

Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

Human Lung-Resident Macrophages Express and Are Targets of Thymic Stromal Lymphopoietin in the Tumor Microenvironment

Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions

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