Targeting the networks that underpin contiguous immunity in asthma and chronic obstructive pulmonary disease.
ABSTRACT Recent advances in the field of innate immunity have driven an important reappraisal of the role of these processes in airway disease. Various strands of evidence indicate that resident cells, such as macrophages and epithelial cells, have central importance in the initiation of inflammation. Macrophage activation has the potential to regulate not just typical aspects of innate immunity but also, via a variety of intricate cell-cell networks, adaptive responses and responses characterized by Th2-type cytokine production. In turn, such adaptive immune processes modify the phenotype and function of the innate immune system. Cooperative responses between monocytic cells and tissue cells are likely to be crucial to the generation of effective inflammatory responses, and a realization of the importance of these networks is providing a new way of identifying antiinflammatory therapies. Importantly, the repeated cycles of allergic and nonallergic inflammation that comprise chronic human airway disease are not necessarily well described by current terminology, and we propose and describe a concept of contiguous immunity, in which continual bidirectional cross-talk between innate and adaptive immunity describes disease processes more accurately.
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ABSTRACT: Removal of disease-driving inflammatory leucocytes is central to resolution of inflammation. The current pharmacological dogma teaches leucocyte elimination through apoptosis followed by phagocytosis. However, actual resolving roles of apoptotic-phagocytic processes have been difficult to demonstrate in the major diseases that are characterized by mucosal tissue inflammation. Many current in vivo observations rather demonstrate that leucocyte elimination occurs by transepithelial locomotion. Findings in diseased gut and bladder mucosae support this notion. Respiratory disease data are particularly compelling. Eosinophils and neutrophils abound in sputum and tracheal aspirates during treatment-induced recovery from severe asthma. Prolonged sputum neutrophilia, along with clinical improvement, follows upon smoking cessation in COPD. Eosinophils, neutrophils, lymphocytes, mast cells and dendritic cells also move in large numbers into the bronchial lumen at spontaneous inflammation resolution following allergen challenge in allergic rhinitis and asthma. A corresponding reduction of infiltrated cells in the bronchial mucosal tissue demonstrates efficiency of the transepithelial elimination pathway. Underscoring its operational role, drugs impeding transepithelial elimination of leucocytes aggravate mucosal/parenchymal inflammation. Hence, relying on lumen cell data alone can lead to paradoxical conclusions regarding anti-inflammatory drug efficacy. Conversely, drugs promoting non-injurious transepithelial elimination of leucocytes could resolve mucosal inflammatory diseases.British Journal of Pharmacology 11/2011; 165(7):2100-9. DOI:10.1111/j.1476-5381.2011.01772.x · 4.99 Impact Factor
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ABSTRACT: Organism-environment interfaces play an essential role in nutriment and gas exchanges. While accomplishing this function, interface tissues must cope with a bacterial, viral and toxic burden. A complex network of interactions between epithelia and immune cells deals with the matter of beneficial versus potentially dangerous signals, resulting in the crucial decision of tolerance induction or breaking. Apart from skin, airway and gastrointestinal epithelia are probably the most important sites of tolerance or sensitisation induction. Because of the complex epithelial–immune cell interplay, experimental settings addressing one cell type are often too simplistic; conversely, ethical as well as methodological issues hamper data collection in humans. Therefore, experimental studies on human complex multicellular in vitro systems should unveil new aspects of the cellular crosstalk in interface tissues.Revue Française d Allergologie 09/2010; 50(5):460-464. DOI:10.1016/j.reval.2010.06.010 · 0.22 Impact Factor
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ABSTRACT: Analysis of exhaled breath condensate (EBC) is a noninvasive method for studying the composition of airway lining fluid and has the potential for assessing lung inflammation. EBC is mainly formed by water vapor, but also contains aerosol particles in which several biomolecules including leukotrienes, 8-isoprostane, prostaglandins, hydrogen peroxide, nitric oxide-derived products, and hydrogen ions, have been detected in healthy subjects. Inflammatory mediators in EBC are detected in healthy subjects and some of them are elevated in patients with different lung diseases. Analysis of EBC is completely noninvasive, is particularly suitable for longitudinal studies, and is potentially useful for assessing the response to pharmacological therapy. Identification of selective profiles of biomarkers of lung diseases might also have a diagnostic value. However, EBC analysis currently has important limitations. The lack of standardized procedures for EBC analysis and validation of some analytical techniques makes it difficult comparison of results from different laboratories. Analysis of EBC is currently more useful for relative measures than for quantitative assessment of inflammatory mediators. Reference analytical techniques are required to provide definitive evidence for the presence of some inflammatory mediators in EBC and for their accurate quantitative assessment in this biological fluid. Several methodological issues need to be addressed before EBC analysis can be considered for clinical applications. However, further research in this area is warranted due to the relative lack of noninvasive methods for assessing lung inflammation.Therapeutic Advances in Respiratory Disease 11/2007; 1(1):5-23. DOI:10.1177/1753465807082373