Mucus Hypersecretion and Eosinophils in Bronchoalveolar Lavage Fluid in Adult Patients with Bronchial Asthma

Tanizaki, Yoshiro; Kitani, Hikaru; Okazaki, Morihiro; Mifune, Takashi; Mitsunobu, Fumihiro; Kimura, Ikuo

doi:10.3109/02770909309054525

Cited by 28 publications

(20 citation statements)

References 18 publications

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“…Therefore, the present findings of a preferential distribution are in line with a role of eosinophils in mucus hypersecretion. This is further supported by other studies showing increased sputum eosinophils during COPD exacerbations [32] and a positive correlation between airway eosinophilia and increased sputum production in asthma [33]. A decrease in the number of eosinophils in the airway wall, especially around the glands, may also contribute to mucus hypersecretion.…”

Section: Discussionsupporting

confidence: 75%

Chronic bronchitis sub-phenotype within COPD: inflammation in sputum and biopsies

Snoeck-Stroband

Lapperre²,

Gosman³

et al. 2007

Eur Respir J

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The presence of chronic bronchitis predicts a more rapid decline of forced expiratory volume in one second (FEV1) in patients with chronic obstructive pulmonary disease (COPD). The hallmark of COPD is airway inflammation. It was hypothesised that COPD patients with chronic bronchitis are characterised by a distinct inflammatory cell profile, as measured in bronchial biopsies and sputum.From 114 COPD patients (male/female ratio 99/15, mean¡SD age 62¡8 yrs, current smoking 63%, post-bronchodilator FEV1 63¡9% predicted, no steroids), with and without chronic bronchitis, inflammatory cell counts in bronchial biopsies and induced sputum were measured. Analysis was carried out by logistic regression.COPD patients with chronic bronchitis had lower eosinophil counts in biopsies and higher percentages of sputum eosinophils than patients without those symptoms, which remained after adjustment for smoking and sex. Patients with chronic bronchitis also showed higher percentages of macrophages and lower percentages of neutrophils in sputum, which could be explained by differences in smoking and sex.It was concluded that chronic bronchitis reflects an inflammatory sub-phenotype among patients with chronic obstructive pulmonary disease. The present results indicate a preferential distribution of eosinophils towards the airway lumen in patients with chronic bronchitis. This may have implications for anti-inflammatory treatment of chronic obstructive pulmonary disease patients with chronic bronchitis.

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Section: Discussionsupporting

confidence: 75%

Chronic bronchitis sub-phenotype within COPD: inflammation in sputum and biopsies

Snoeck-Stroband

Lapperre²,

Gosman³

et al. 2007

Eur Respir J

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“…The novel findings in this study are consistent with a previous report showing that human eosinophils induce mucin production in airway epithelial cells via EGFR activation in NCI-H292 cells [12] . In addition, a positive correlation has been shown between eosinophilia and increased sputum production in asthma [18] , suggesting that eosinophilia might be involved in mucus hypersecretion. Furthermore, Elovic et al [19] have reported that TGF-␣ production by eosinophils is upregulated by IL-3 and IL-5, but downregulated by IL-4.…”

Section: Discussionmentioning

confidence: 99%

The Role of Transforming Growth Factor-α on Mucin Overproduction in Eosinophilic Chronic Rhinosinusitis

Ishinaga¹,

Shah²,

Sakaida³

et al. 2011

Pharmacology

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Objectives: Eosinophilic chronic rhinosinusitis (ECRS) is considered a refractory and intractable disease with thick mucus production, long-term nasal congestion, loss of sense of smell and intermittent acute exacerbations secondary to bacterial infections. In this study, we investigated which growth factor is deeply involved in the mucin overproduction in ECRS. Method: We employed fluorescence immunohistochemical analysis to evaluate whether or not TGF-α expression was upregulated in the nasal tissue of ECRS patients. We also examined MUC5AC transcription using a luciferase reporter plasmid in HM3-MUC5AC cells and A549 cells in order to assess the role of TGF-α in human epithelial cells. Results: TGF-α immunoreactivity was found markedly increased in the submucosal tissue in the ECRS patient compared with that of a normal patient and with noneosinophilic CRS. TGF-α synergized with TNF-α to upregulate MUC5AC expression in human epithelial cells through the ERK signaling pathway. Conclusion: Our results demonstrated that TGF-α was highly expressed in the upper airway tract in ECRS patients and is deeply involved in mucus hypersecretion.

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“…Previous studies reported a positive correlation between eosinophilia (in blood (37) and in airways (8)) and increased sputum production in asthma, suggesting that eosinophils might be involved in mucus hypersecretion. Similarly, in chronic obstructive pulmonary disease, Saetta et al (38) reported increased numbers of sputum eosinophils during exacerbations, and Haraguchi et al (39) reported a positive correlation between airway eosinophils and the presence of goblet cell metaplasia in patients dying of asthma-like attacks.…”

Section: Discussionmentioning

confidence: 99%

“…Excessive mucus production from hyperplastic goblet cells is also reported in acute (3) and chronic (4,5) asthma and in nasal polyps (6). Human tissues in fatal asthma are reported to show extensive eosinophil degranulation, especially in mucus plugs and in surface epithelium (7), and a positive correlation between eosinophil counts in bronchoalveolar lavage fluid and sputum production has been reported in asthmatic patients (8). Because Ag challenge in animal models of allergic asthma resulted in marked eosinophilic airway inflammation and goblet cell metaplasia (9), it was suggested that eosinophils play a role in mucus production in allergic diseases.…”

mentioning

confidence: 99%

Human Eosinophils Induce Mucin Production in Airway Epithelial Cells Via Epidermal Growth Factor Receptor Activation

Burgel

Lazarus

Tam

et al. 2001

The Journal of Immunology

135

101

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Eosinophil recruitment and mucus hypersecretion are characteristic of asthmatic airway inflammation, but eosinophils have not been shown to induce mucin production. Because an epidermal growth factor receptor (EGFR) cascade induces MUC5AC mucin in airways, and because EGFR is up-regulated in asthmatic airways, we examined the effect of eosinophils on MUC5AC mucin production in NCI-H292 cells (a human airway epithelial cell line that produces mucins). Eosinophils were isolated from the peripheral blood of allergic patients, and their effects on MUC5AC mucin gene and protein synthesis were assessed using in situ hybridization and ELISAs. When IL-3 plus GM-CSF or IL-3 plus IL-5 were added to eosinophils cultured with NCI-H292 cells, MUC5AC mucin production increased; eosinophils or cytokines alone had no effect. Eosinophil supernatant obtained by culturing eosinophils with IL-3 plus GM-CSF or IL-3 plus IL-5 also increased MUC5AC synthesis in NCI-H292 cells, an effect that was prevented by selective EGFR inhibitors (AG1478, BIBX1522). Supernatant of activated eosinophils induced EGFR phosphorylation in NCI-H292 cells. Supernatant of activated eosinophils contained increased concentrations of TGF-α protein (an EGFR ligand) and induced up-regulation of TGF-α expression and release in NCI-H292 cells. A blocking Ab to TGF-α reduced activated eosinophil-induced MUC5AC synthesis in NCI-H292 cells. These results show that activated eosinophils induce mucin synthesis in human airway epithelial cells via EGFR activation, and they implicate TGF-α produced by eosinophils and epithelial cells in the EGFR activation that results in mucin production in human airway epithelium.

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Mucus Hypersecretion and Eosinophils in Bronchoalveolar Lavage Fluid in Adult Patients with Bronchial Asthma

Cited by 28 publications

References 18 publications

Chronic bronchitis sub-phenotype within COPD: inflammation in sputum and biopsies

Chronic bronchitis sub-phenotype within COPD: inflammation in sputum and biopsies

The Role of Transforming Growth Factor-α on Mucin Overproduction in Eosinophilic Chronic Rhinosinusitis

Human Eosinophils Induce Mucin Production in Airway Epithelial Cells Via Epidermal Growth Factor Receptor Activation

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