Transcriptional profiling of circulating mononuclear cells from patients with chronic obstructive pulmonary disease receiving mesenchymal stromal cell infusions

The pathogenesis of chronic obstructive pulmonary disease is not fully understood. The objective of this study was to compare circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease to age, sex, and cigarette smoking matched healthy controls. Patients with chronic obstructive pulmonary disease ( n = 37) and healthy controls ( n = 19) were matched by age, sex, and smoking status. Circulating hematopoietic progenitor cells (CD34+ or CD133+ mononuclear cells) and endothelial progenitor cells (CD34+KDR+ or CD34+CD133+KDR+ mononuclear cells) were quantified by flow cytometry. Endothelial cell-colony forming units from peripheral blood mononuclear cells were quantified in vitro and phenotypic analysis carried out using immunocytochemistry. Patients with chronic obstructive pulmonary disease had more circulating mononuclear cells compared with controls (8.4 ± 0.6 vs. 5.9 ± 0.4 × 109 cells/l; P = 0.02). CD34+ hematopoietic progenitor cells were reduced as a proportion of mononuclear cells in patients compared with controls (0.99 ± 0.12 vs. 1.9 ± 0.12%; P = 0.02); however, there were no differences in the absolute number of CD34+, CD34+KDR+, or CD34+CD133+KDR+ cells ( P > 0.05 for all). Endothelial cell-colony forming units were increased in patients with chronic obstructive pulmonary disease compared with controls (13.7 ± 5.2 vs. 2.7 ± 0.9 colonies; P = 0.048). In contrast to previous studies, the number of circulating progenitor cells was not reduced in patients with chronic obstructive pulmonary disease compared with carefully matched controls. It seems unlikely that circulating endothelial progenitor cells or failure of angiogenesis plays a central role in the development of emphysema.

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Exploration on the regulatory mechanisms of MBD2/miR-301a-5p/CXCL12/CXCR4 on acute exacerbations of chronic obstructive pulmonary disease

10.21203/rs.3.rs-25344/v1 ◽

2020 ◽

Author(s):

Wen Shen ◽

Zhiyin Weng ◽

Minjuan Fan ◽

Shukun Wang ◽

Ruili Wang ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Mononuclear Cells ◽

Airflow Obstruction ◽

Expression Level ◽

Clinical Samples ◽

Chronic Obstructive ◽

Cxcl12 Expression ◽

Obstructive Pulmonary Disease ◽

Acute Exacerbations

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by irreversible expiratory airflow obstruction and its chronic course is worsened by recurrent acute exacerbations. Our previous microarray identified miR-301a-5p was associated with the progression of AE-COPD, but its regulatory mechanism underlying COPD pathogenesis remains uncovered.Methods Serum and peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and patients with COPD in remission (R-COPD) and acute exacerbation (AE-COPD). Human HULEC-5a and HBE cells were transfected with MBD2, sh-MBD2, miR-301a-5p mimics or inhibitor, followed by stimulated with cigarette smoke extract (CSE). The co-culture assays were performed by the addition of the supernatant of medium derived from HULEC-5a cells transfected with miR-301a-5p mimics or inhibitor into si-CXCR4-transfected-lung fibroblast or THP-1 macrophages. Transwell assay was used to analyze cell migration.Results Clinical samples showed that decreased miR-301a-5p level in AE-COPD was significantly positively correlated with the expression level of MBD2, but negatively correlated with CXCL12 expression level. MBD2 overexpression significantly promoted miR-301a-5p, while suppressed CXCL12 in HULEC-5a and HBE cells. CXCL12 was confirmed as a direct target of miR-301a-5p. CXCR4 knockdown significantly the suppressive effect of miR-301a-5p mimics and attenuated the promotional effects of miR-301a-5p inhibitor on the migration of circulating fibroblasts and macrophages, as well as the expression levels of P-MEK and P-AKT.Conclusion In summary, MBD2/miR-301a-5p/CXCL12/CXCR4 appears to be involved in such recruitments of circulating fibroblasts and macrophages during COPD exacerbations.

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Decreased NF-ºB Repressing Factor In Circulating Mononuclear Cells From Patients With Chronic Obstructive Pulmonary Disease Is Accociated With Enhanced Release Of IL-8/CXCL8

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a2680 ◽

2010 ◽

Author(s):

Kang-Yun Lee ◽

Shu-Chuan Ho ◽

Y.-F. Chan ◽

Ya-Ling Chang ◽

Lu-Wei Kuo ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Mononuclear Cells ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

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Eﬀect of the combination of theophylline and budesonide on production of proinﬂammatory cytokines by blood cells of patients with chronic obstructive pulmonary disease

Tuberculosis and lung diseases ◽

10.21292/2075-1230-2021-99-10-14-22 ◽

2021 ◽

Vol 99 (10) ◽

pp. 14-22

Author(s):

A. G. Kadushkin ◽

A. D. Taganovich ◽

L. V. Movchan ◽

E. I. Talabaeva ◽

A. V. Plastinina ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

T Lymphocytes ◽

Pulmonary Disease ◽

Cytotoxic T Lymphocytes ◽

Proinflammatory Cytokines ◽

Blood Cells ◽

Mononuclear Cells ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

T Helpers

The objective: to evaluate the ability of the combination of theophylline and budesonide to suppress proinﬂammatory cytokine production byblood cells in patients with chronic obstructive pulmonary disease (COPD).Subjects and Methods. Peripheral blood mononuclear cells (PBMCs) or whole blood cells of COPD patients (n = 27) were incubated with budesonide (10 nM), theophylline (1 μM), or the combination thereof and stimulated with phytohemagglutinin (PHA) or phorbol myristate acetate (PMA) and ionomycin. The enzyme immunoassay was used to evaluate the secretion of thymic stromal lymphopoietin (TSLP), macrophage migration inhibitory factor (MIF), interleukin 17A (IL-17A), IL-33, and other mediators of PBMC cells, and induced PHA. The ﬂow cytometry was used to analyze intracellular production of proinﬂammatory cytokines stimulated by PMA/ionomycin in T-helpers (CD4+) and cytotoxic T-lymphocytes (CD8+).Results. Theophylline reduced the secretion of IL-4 and IL-17A by PBMC cells. The combination of budesonide with theophylline inhibited the synthesis of IL-4, IL-5, IL-8, IL-13, IL-17A, IL-33, TSLP, MIF by PBMC cells as well as the production of IL-4, IL-8, tumor necrosis factor-α, and interferon-γ by cytotoxic T-lymphocytes and T-helpers. The combination of theophylline and budesonide had a more pronounced inhibitory eﬀect on the production of IL-4 and IL-8 by PBMC cells as well as the synthesis of IL-4 by CD4+ T-cells and IL8 by CD8+ T-lymphocytes versus the eﬀect of monotherapy with budesonide.

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Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

American Journal of Speech-Language Pathology ◽

10.1044/2019_ajslp-19-00095 ◽

2020 ◽

Vol 29 (2) ◽

pp. 864-872

Author(s):

Fernanda Borowsky da Rosa ◽

Adriane Schmidt Pasqualoto ◽

Catriona M. Steele ◽

Renata Mancopes

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Oral Cavity ◽

Pulmonary Disease ◽

Thermal Sensation ◽

Sensory Function ◽

Control Group ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Age Related ◽

Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

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