Airway generation‐specific differences in the spatial distribution of immune cells and cytokines in allergen‐challenged rhesus monkeys

Miller, Lisa; Hurst, Stephen D.; Coffman, Robert L.; Tyler, Nancy K.; Stovall, Mary Y.; Chou, Debbie L.; Putney, Lei; Gershwin, Laurel J.; Schelegle, Edward S.; Plopper, Charles G.; Hyde, Dallas M.

doi:10.1111/j.1365-2222.2005.02271.x

Cited by 44 publications

(57 citation statements)

References 64 publications

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“…It is possible that a different inflammatory milieu exists in the airways, with a gradient in cytokine expression. Using an allergen-induced asthma model in rhesus monkeys, Miller et al [27] reported increased levels of cytokines and chemokines within the distal lung, whereas CD4+ lymphocytes accumulated preferentially in the proximal to midlevel region of the lungs. The authors proposed that the distal lung may be involved in the mobilisation of effector immune cells into the airways and that the proximal airways may serve as a reservoir for immune cells that contribute to chronic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

et al. 2011

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Background: Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airway obstruction. Smoking causes persistent inflammation in lung tissue. However, differences in inflammatory responses between the large and small airways have not been systematically explored among smokers with and without COPD. Objectives: The aim of our research was to characterise the expression and localisation of NF-ĸBp65 and histone deacetylase 2 (HDAC2) as well as inflammatory cell (macrophages, lymphocytes, neutrophils) distribution in large and small airways, in nonsmokers and in smokers with and without COPD. Methods: Nineteen nonsmokers, 20 smokers with normal lung ventilation function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate NF-ĸBp65 and HDAC2 expression and identify inflammatory cells in airways. Results: COPD patients had increased NF-ĸBp65 expression compared to nonsmokers and smokers without COPD, in both large and small airways, which corresponded to increased numbers of macrophages, CD8+ T lymphocytes and neutrophils. COPD patients had more macrophages in large compared to small airways and more CD8+ T lymphocytes and neutrophils in small compared to large airways. HDAC2 expression was significantly downregulated in smokers with COPD in small compared to large airways. Conclusions: Our findings indicate a nonuniform distribution of inflammatory cells throughout the bronchial tree. However, in both smokers with and without COPD, similar patterns of inflammatory processes occur in both large and small airways. The difference between smokers with and without COPD is only quantitative.

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Section: Discussionmentioning

confidence: 99%

Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

et al. 2011

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“…1,2 The disease is characterized by airflow obstruction that varies over time and in response to treatment 3,4 and by airway hyperresponsiveness to stimuli, such as allergens, irritants, cold air, and viruses. Histologic studies performed in patients who died during an acute asthma attack have shown that the inflammatory changes within the lungs of patients with asthma are heterogeneously distributed throughout the lungs.…”

mentioning

confidence: 99%

The variability of regional airflow obstruction within the lungs of patients with asthma: Assessment with hyperpolarized helium-3 magnetic resonance imaging

Lange¹,

Altes²,

Patrie³

et al. 2007

Journal of Allergy and Clinical Immunology

160

140

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“…All of these cell types accumulate within airways in unique patterns of distribution, suggesting compartmentalised responses with regard to trafficking. Although cytokine mRNA levels are elevated throughout the conducting airway tree of HDMA-challenged animals, the distal airways (terminal and respiratory bronchioles) exhibit the most pronounced upregulation [73].…”

Section: Airway Physiologymentioning

confidence: 99%

Asthma: a comparison of animal models using stereological methods

et al. 2006

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Asthma is a worldwide health problem that affects 300 million people, as estimated by the World Health Organization. A key question in light of this statistic is: ''what is the most appropriate laboratory animal model for human asthma?''The present authors used stereological methods to assess airways in adults and during postnatal development, and their response to inhaled allergens to compare rodents and nonhuman primates to responses in humans.An epithelial-mesenchymal trophic unit was defined in which all of the compartments interact with each other. Asthma manifests itself by altering not only the epithelial compartment but also other compartments (e.g. interstitial, vascular, immunological and nervous). All of these compartments show significant alteration in an airway generation-specific manner in rhesus monkeys but are limited to the proximal airways in mice. The rhesus monkey model shares many of the key features of human allergic asthma including the following: 1) allergen-specific immunoglobulin (Ig)E and skin-test positivity; 2) eosinophils and IgE+ cells in airways; 3) a Thelper type 2 cytokine profile in airways; 4) mucus cell hyperplasia; 5) subepithelial fibrosis; 6) basement membrane thickening; and 7) persistent baseline hyperreactivity to histamine or methacholine.In conclusion, the unique responses to inhaled allergens shown in rhesus monkeys make it the most appropriate animal model of human asthma.

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Airway generation‐specific differences in the spatial distribution of immune cells and cytokines in allergen‐challenged rhesus monkeys

Cited by 44 publications

References 64 publications

Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

The variability of regional airflow obstruction within the lungs of patients with asthma: Assessment with hyperpolarized helium-3 magnetic resonance imaging

Asthma: a comparison of animal models using stereological methods

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