Adenosine and its receptors : translational studies in asthma and COPD

We were the first to report studies regarding adenosine receptor expression on inflammatory cells in peripheral blood and sputum in asthma patients and healthy controls, as well as sputum of COPD patients and asymptomatic smokers. With these results we partly addressed the difficulties presented in the conclusions part of chapter 2 of this thesis (29). Here we stated: "Thus far, the exact distribution and function of the different adenosine receptor subtypes in human airways remains largely unknown and this makes it difficult to establish which (combination of) receptors should be targeted" Our studies have increased our knowledge about adenosine receptor expression and distribution in healthy and disease situations which could already give some indications about treatment directions. With respect to asthma, we showed as anticipated that asthma patients have an increased number of eosinophils in peripheral blood and induced sputum, and that these numbers further increased in sputum after allergen challenge. However, AR expression on blood eosinophils in asthma did not differ from that in healthy controls nor did it change upon allergen challenge, thus not explaining this increased eosinophil migration. Furthermore, we were not able to evaluate AR expression on sputum eosinophils because only few asthma patients had sufficient numbers of eosinophils in sputum to perform reliable scoring. Thus, it appears that allergen challenge does not directly affect eosinophil recruitment via adenosine receptor stimulation to the lung tissue, and other indirect factors like mediator release from mast cells, epithelial cells and other resident or inflammatory cells thus likely contribute to eosinophils attraction. Since an important role in chemotaxis is described especially for A3R on eosinophils (29), it would be of importance to include determination of the expression of this receptor in future studies (e.g. by performing eosinophil purification of the sputum samples before cytospin preparation).