Distinct amplification of the C5a-receptor pathways in normodense and hypodense eosinophils of patients with atopic dermatitis

In patients with atopic dermatitis two different types of blood eosinophils with distinct density can be isolated. The normodense cells represent the huge majority in count, whereas the hypodense eosinophils are characterized by higher effector activity. To understand the altered functional responsi veness of these two cell subtypes, the expression of C5a receptors as well as C5a-induced signal pathways and the production of reactive oxygen metabo lites have been analyzed. Chemiluminescence measurements revealed significa nt higher production of reactive oxygen metabolites in hypodense eosinophil s in comparison to normodense cells. However, no difference in the expressi on level of C5a receptors as well as in the C5a-induced Ca2+-transients bet ween normodense and hypodense eosinophils were found. In contrast, hypodens e eosinophils showed a significantly higher actin polymerization response a nd phosphatidylinositol 4,5 bisphosphate 3-kinase activation after stimulat ion with C5a than normodense eosinophils. Therefore, normodense and hypoden se eosinophils from the blood of patients with atopic dermatitis are charac terized by differential amplification of C5a-receptor signal pathways, whic h might explain the differences in their proinflammatory activity.