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Regulation of the Release of Inflammatory Mediators From Lung Macrophages.

NCT00147017 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 17

Last updated 2019-12-10

Study results available
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Summary

The aim of this study is to investigate the mechanisms whereby specific white cells called macrophages found in the lung release inflammatory mediators or chemicals together with enzymes that destroy the surrounding lung tissue. The hypothesis is that in diseases such as chronic obstructive pulmonary disease (COPD), lung macrophages release either more or different types of inflammatory mediators and/or destructive enzymes compared to subjects without COPD. We will isolate macrophages from small pieces of lung parenchyma. These samples are derived from lobes resected for carcinoma of the lung. We would aim to examine the responses of tissue derived macrophages in three groups of subjects, namely (i) non-smoking controls (lung carcinoma as secondary metastasis), (ii) smokers without clinical or histological signs of COPD and (iii) smokers with COPD. The resected lung tissue will be cut into small pieces and washed in order to release the macrophages from the tissue. The macrophages will then be isolated from other cell types in the washings. We will then use these isolated cells in vitro to examine the cell surface receptors in order to compare these macrophage cells with macrophages reported from bronchoalveolar lavage and monocyte derived macrophage models. We will then examine inflammatory mediator synthesis and release following stimulation of these cells. We will also examine the regulation and release of enzymes known to damage lung tissue. Using these two models we will then examine the signal transduction pathways that lead to this activation of the macrophages and investigate the effects of novel therapeutic agents to inhibit inflammatory mediator and/or enzyme synthesis and release. The objective is to identify the mechanisms whereby macrophages respond to pro-inflammatory conditions seen in COPD with a view to identify novel targets for drug therapy.

Conditions

  • COPD
  • Chronic Bronchitis
  • Emphysema

Sponsors & Collaborators

  • Novartis

    collaborator INDUSTRY

  • Boehringer Ingelheim

    collaborator INDUSTRY

  • Royal Brompton & Harefield NHS Foundation Trust

    collaborator OTHER

  • Imperial College London

    lead OTHER

Principal Investigators

  • Louise E Donnelly, PhD · Imperial College London

Eligibility

Min Age
21 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2001-06-30
Primary Completion
2010-12-31
Completion
2010-12-31

Countries

  • United Kingdom

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00147017 on ClinicalTrials.gov