The contribution of neurotrophins to the pathogenesis of allergic asthma

2006 ◽  
Vol 34 (4) ◽  
pp. 594-599 ◽  
Author(s):  
S. Rochlitzer ◽  
C. Nassenstein ◽  
A. Braun

The neurotrophins nerve growth factor, brain-derived neurotrophic factor, NT-3 (neurotrophin 3) and NT-4 are known for regulating neuron development, function and survival. Beyond this, neurotrophins were found to exert multiple effects on non-neuronal cells such as immune cells, smooth muscle and epithelial cells. In allergic asthma, airway inflammation, airway obstruction, AHR (airway hyperresponsiveness) and airway remodelling are characteristic features, indicating an intensive interaction between neuronal, structural and immune cells in the lung. In allergic asthma patients, elevated neurotrophin levels in the blood and locally in the lung are commonly observed. Additionally, structural cells of the lung and immune cells, present in the lung during airway inflammation, were shown to be capable of neurotrophin production. A functional relationship between neurotrophins and the main features of asthma was revealed, as airway obstruction, airway inflammation, AHR and airway remodelling were all shown to be stimulated by neurotrophins. The aim of the present review is to provide an overview of neurotrophin sources and target cells in the lung, concerning their possible role as mediators between structural cells, immune cells and neurons, connecting the different features of allergic asthma.

2017 ◽  
Vol 8 (12) ◽  
pp. 4315-4324 ◽  
Author(s):  
Sara L. Coleman ◽  
Odette M. Shaw

The potential of fruit proanthocyanidins to modulate airway inflammation through interactions with immune cells and the microbiome.


2017 ◽  
Vol 1 (S1) ◽  
pp. 3-3
Author(s):  
Timothy P. Moran ◽  
Robert M. Immormino ◽  
Hideki Nakano ◽  
David Peden ◽  
Donald N. Cook

OBJECTIVES/SPECIFIC AIMS: Allergic asthma is a chronic lung disease driven by inappropriate inflammatory responses against inhaled allergens. Neuropilin-2 (NRP2) is a pleiotropic transmembrane receptor expressed in the lung, but its role in allergic airway inflammation is unknown. Here, we characterized NRP2 expression in lung immune cells and investigated the effects of NRP2 deficiency on airway inflammation. METHODS/STUDY POPULATION: NRP2 expression by lung immune cells from NRP2 reporter mice was determined by flow cytometry. NRP2 expression by human alveolar macrophages (AM) from healthy individuals was determined by mRNA analysis and flow cytometry. Airway inflammation in NRP2-deficient mice was assessed by bronchoalveolar lavage (BAL) cytology and inflammatory gene expression in lung tissue. RESULTS/ANTICIPATED RESULTS: NRP2 expression in lung immune cells was negligible under steady-state conditions. In contrast, inhalational exposure to lipopolysaccharide (LPS) adjuvant dramatically induced NRP2 expression in AM, as 63.3% of AM from LPS-treated mice were NRP2+ compared with 1.5% of AM from control mice. Ex vivo treatment of human AM with LPS resulted in a 1.5-fold and 2.6-fold increase in NRP2 mRNA and surface protein expression, respectively. Compared to littermate controls, NRP2-deficient mice had greater numbers of BAL leukocytes and increased lung expression of the T helper type 2 cytokines IL-4 and IL-5. Furthermore, NRP2 deficiency resulted in stochastic development of allergic airway inflammation, as spontaneous airway eosinophilia was detected in 25% (2/8) of NRP2-deficient mice compared with 0% (0/8) of littermate controls. DISCUSSION/SIGNIFICANCE OF IMPACT: NRP2 is expressed by activated human and murine AM and suppresses the spontaneous development of allergic airway inflammation. These findings suggest that NRP2 may play a key role in allergic asthma pathogenesis, and could prove to be an important therapeutic target in patients with asthma and other allergic diseases.


Author(s):  
Fortune O Alabi

Objective: In this study, we: (1) evaluated the correlation between total IgE and the presence of specific IgE; (2) compared the characteristics of patients with positive specific IgE to those with negative specific IgE; and, (3) analyzed the allergic testing results of patients on omalizumab and reported the effect of omalizumab on forced expiratory volume (FEV1) and asthma control test (ACT) results. Methods: Data from patients diagnosed with allergic asthma and seen at Florida Lung, Asthma & Sleep Specialists (FLASS) between January 2016 and June 2019 were analyzed. Parameters evaluated were total IgE, and levels of specific IgE to antigens in the ImmunoCAP test and skin prick test (SPT). Additional parameters for patients on omalizumab therapy for at least 6 months were FEV1, % predicted FEV1 and ACT results. Results: A total of 475 patients (114 males, 361 females) met the inclusion criteria. The mean age was 53 years (range: 17 to 89 years). Of these, 36 patients were not included in the analysis due to incomplete data. Mean total IgE was higher in patients with positive ImmunoCAP results compared to those with negative results (396 KU/L vs. 81.3 KU/L). There was a significant positive correlation between total IgE and levels of positive specific IgE in the ImmunoCAP test (p<0.0001, r=0.36, n=213 patients). The correlation between total IgE and levels of positive allergens in SPT was not significant (p=0.15, n=44 patients) Two positive reactions to allergens were seen in 22% of ImmunoCAP tests and 13% of SPT tests. There was no statistically significant improvement in FEV1 (p=0.097, CI -0.17 to 0.02) and % predicted FEV1 (p=0.109, CI -6.63 to 0.70) in patients who used omalizumab for at least 6 months. There was a statistically significant improvement in ACT scores (p=0.031, CI -4.21 to -0.21) in patients who used omalizumab for at least 6 months. Conclusion: Allergic asthma could be seen in patients who had an absence of specific IgE in ImmunoCAP and a negative reaction to SPT. The benefit of omalizumab therapy is not limited to allergic asthma patients with positive specific IgE.


2019 ◽  
Vol 20 (10) ◽  
pp. 799-803 ◽  
Author(s):  
Meizhen Zhao ◽  
Yu-Pei Li ◽  
Xiao-Rui Geng ◽  
Miao Zhao ◽  
Shi-Bo Ma ◽  
...  

Background: To investigate MiRNA-126 amounts in serum exosomes from allergic asthma patients as well as lung tissues of asthmatic mice, evaluating the expression of its target gene DNMT1 in mouse specimens. Methods: MiRNA-126 amounts in serum exosomes from asthmatic patients were detected by real-time PCR. The mouse model of allergic asthma was established by OVA-sensitization, and allergic symptoms were recorded; serum IL-4 and sIgE level evaluation (ELISA), broncho alveolar lavage fluid (BALF) cell count and H&E staining were performed to assess airway inflammation. MiRNA-126 and DNMT1 levels in the lung of asthmatic and control mice were detected by real-time PCR; DNMT1 protein levels were detected by immunoblot. Results: MiRNA-126 amounts in peripheral blood exosomes from patients with allergic asthma were significantly higher than that of healthy volunteers (P<0.05). The frequencies of scratching of both sides of the nose and sneezing were elevated within 10 min of excitation in asthmatic rats compared with controls. Meanwhile, OVA-sIgE and IL-4 levels were significantly higher in asthmatic animals than controls (P<0.05). In the asthma group, narrowed bronchial lumen and thickened wall were observed, and bronchial and peripheral vessels showed overt inflammatory cell infiltration. Eosinophil, neutrophil and mast cell amounts in the BALF of asthmatic mice were significantly higher than control values. Furthermore, lung miRNA-126 expression in asthmatic mice was significantly higher than that of controls. Finally, DNMT1 mRNA and protein levels were significantly lower in asthmatic animals compared with controls (P < 0.01). Conclusion: MiRNA-126 is highly expressed in serum exosomes from allergic asthma patients and lung tissues of asthmatic mice, suggesting that it may be involved in the pathogenesis of bronchial asthma.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 263
Author(s):  
Philip Rosenstock ◽  
Thomas Kaufmann

Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and tumor cells. Sialic acids can influence the interaction of NK cells with potential targets in several ways. Different NK cell receptors can bind sialic acids, leading to NK cell inhibition or activation. Moreover, NK cells have sialic acids on their surface, which can regulate receptor abundance and activity. This review is focused on how sialic acids on NK cells and their target cells are involved in NK cell function.


Author(s):  
Matthew C. Altman ◽  
Agustin Calatroni ◽  
Sima Ramratnam ◽  
Daniel J. Jackson ◽  
Scott Presnell ◽  
...  

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Yi Jiang ◽  
Ruoli An ◽  
Li Cheng ◽  
Qianru Yue ◽  
Hanwei Zhang ◽  
...  

Abstract Background Investigating the endotypes of the different asthma phenotypes would help disease monitoring, prognosis determination, and improving asthma management standardization. This study aimed to classify asthma into four endotypes according to the allergic and eosinophilic characteristics and explore the phenotypes (clinical characteristics, pulmonary functions, and fractional expired nitric oxide (FeNO)) of each endotype. Methods This retrospective study included non-acute asthma patients treated at the First Hospital of Shanxi Medical University (05/2016–01/2018). The patients were classified into the eosinophilic allergic, eosinophilic non-allergic, non-eosinophilic allergic, and non-eosinophilic non-allergic asthma endotypes. Serum sIgE, lung function, FeNO, and induced sputum cytology were tested and compared among groups. Results Of the 171 included patients, 22 had eosinophilic allergic asthma, 17 had eosinophilic non-allergic asthma, 66 had non-eosinophilic allergic asthma, and 66 had non-eosinophilic non-allergic asthma. Lung function measurements (FEV1%, FEF25%, FEF50%, FEF75%, and FEF25–75%) showed that airway dysfunction was worse in eosinophilic non-allergic asthma than in the other three endotypes (all P < 0.001). In allergic asthma patients, eosinophilic asthma had worse airway dysfunction than non-eosinophilic asthma (all P < 0.05). Similar results were found in non-allergic asthma (all P < 0.01). The FeNO levels in eosinophilic allergic asthma were higher than in eosinophilic non-allergic and non-eosinophilic non-allergic asthma (both P = 0.001). Conclusions FeNO can objectively reflect eosinophilic airway inflammation in asthma. Endotypic classification of asthma patients regarding the allergic and eosinophilic characteristics is conducive to the effective management of patients with asthma.


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