Peripheral blood intermediate monocyte PAR-2 expression increases during asthma exacerbations and following inhalation allergen challenge

Myeloid cells, especially dendritic cells and macrophages play important roles in asthma pathophysiology. Monocytes (Mo) and macrophages express PAR-2, a pro-inflammatory serine protease receptor implicated in the pathophysiology of allergic airway inflammation. We have shown that patients with severe asthma and those with a history of frequent asthma exacerbations exhibit increased PAR-2 expression on peripheral blood monocytes. The study aims to determine PAR-2 expression on peripheral blood intermediate monocytes (IMMo) in subjects with increased airway inflammation, either as a result of an asthma exacerbation or following an inhalation allergen challenge. Sixteen adults presenting to the emergency department (ED) with asthma exacerbations were recruited after giving informed consent. Ten patients returned 2 weeks later for follow-up. Eleven mild asthmatics treated only with as needed bronchodilators were recruited and underwent inhalation allergen challenge after informed consent. Immune cell profiling was performed by whole blood flow cytometry in both groups of patients. PAR-2 expression in peripheral blood IMMo was increased in patients with an asthma exacerbation compared to patients with stable disease and this expression decreased following treatment of the asthma exacerbation. Subjects with mild asthma showed increase in percentages of IMMo expressing PAR-2 after allergen challenge. Patients presenting to the ED, had lower dendritic cell (DC) and DC subset numbers in peripheral blood during exacerbation compared to after treatment. Increased PAR-2 expression on Mo during periods of increased airway inflammation may initiate a positive feedback loop leading to systemic inflammatory changes.