Neutrophil and eosinophil chemotaxins in asthma

Abstract

Despite the development of sophisticated drugs for the treatment of asthma, its prevalence and severity may be increasing. Although the environment appears to be the major factor underlying the rising trend, great emphasis has recently been put on studying the genetics of this disease. It is well recognized that most asthma in children and young adults is associated with atopy, characterized by an increased synthesis of IgE against common allergens. Exposure of these patients to specific aeroallergens consequently initiates a series of immunological changes, culminating in airway inflammation. The application of fibre-optic bronchoscopy to obtain mucosal lavage and biopsy material from the airways has reaffirmed the view that airway inflammation underlies disordered airway function, even in mild asthma. Careful analysis of this material has revealed striking infiltration of eosinophils and other cell types into the airways of these patients. Although eosinophils are predominantly involved in asthma, neutrophils also participate both in occupational asthma and during the late asthmatic response following antigen challenge. One reason for the presence of neutrophils and eosinophils at the site of inflammation is the local generation of chemotactic agents that direct cell migration from the blood vessels into the bronchial mucosa. The first step in this migration is the margination and adherence of the cell to the blood vessel wall. Leukocytes adhere using molecules present on the luminal surface of endothelium, which are upregulated as a result of chemoattractant cytokine release (Figure 2). This article reviews what is known about the factors involved in the recruitment of neutrophils and eosinophils. Neutrophil chemoattractants will be considered first, then eosinophil chemoattractants, and then the role of these chemoattractants in endothelial cell adherence.