Editorial [Hot Topic: Granulocyte Toxicity in the Lung (Guest Editor: Hannu Kankaanranta)]

The role of the eosinophil in the pathogenesis of asthma was recently questioned by studies with anti-cytokine therapies that reduced the number of circulating eosinophils dramatically, but failed to affect the clinical measures of asthma. Although of ultimate importance to this field, those findings led to a dramatic halt in the development programs for anti-eosinophil based therapies for asthma and allergy. However, more recent studies showed that a decrease in peripheral blood eosinophil count does not lead to clearance of eosinophils or their granule products from the lungs of patients with asthma. Rather than casting doubt to the role of eosinophil in asthma, recent evidence further strengthens the role of eosinophil both as an effector cell and in orchestrating the immunological events central to asthma. It appears that not only the eosinophil, but also the neutrophil may play a role in the pathogenesis of moderate to severe asthma. Neutrophils are considered to be important effectors in the pathogenesis of COPD. However, recent evidence implicates a role for eosinophils also in COPD, especially during the COPD exacerbations. Now we are living a time of reappraisal of the importance of granulocytes, both the eosinophil and the neutrophil, in the pathogenesis of asthma and COPD. Thus it is time to critically evaluate the recent advances in eosinophil and neutrophil biology and their clinical correlates and to evaluate the avenues for future drug development to limit the toxicity of granulocytes in the lung. Eosinophils and neutrophils are both terminally differentiated granulocytes, which are able to produce several proinflammatory mediators and reactive oxygen species. Increase in nitric oxide production by inducible nitric oxide synthase has been shown to occur in asthma. Thus, in addition to their own production of reactive oxygen (ROS) and/or nitrogen species (RNS), granulocytes are exposed to reactive oxygen and nitrogen metabolites produced by other cells or tobacco smoke in the lung. Thus, it is important to understand the signalling related to ROS/RNS and regulation of their production as well as means to protect from their effects. The numbers of eosinophils and neutrophils in the lung are regulated by several factors, namely the balance of recruitment and migration of granulocytes to the lung and removal of granulocytes from the lung. Identification of eosinophil cytolysis in asthmatic airways, leading to the release of toxic eosinophil contents and/or free eosinophil granules to the surrounding tissues serves as a background why we should seek for the mechanisms and ways how to clear the lung from eosinophils and/or neutrophils. Thus several groups focus on finding the mechanisms how granulocyte apoptosis is controlled and seek potential drug targets to selectively remove eosinophils and /or neutrophils from the asthmatic or allergic airways to reduce their toxicity. To achieve these goals, we also need to learn how the currently used anti-inflammatory medication, especially the glucocorticoids, affect granulocytes and what is the contribution of eosinophils and neutrophils to the clinical presentation of asthma and COPD. I hope that this special theme issue on “Control of granulocyte toxicity in the lung” will provide the reader with an update on the current knowledge in controlling eosinophil and neutrophil toxicity in the lung. Finally, I would like to thank all the authors, who represent some of the most prominent groups in this field, for contributing to this Hot Topic issue.