The effect of cationic charge on release of eosinophil mediators

Abstract

Background: In patients with atopic diseases, cationic-charged eosinophil proteins are deposited in inflamed tissues. Although the role of cytokines in cell activation is well established, the presence of cationic-charged tissue can also be an important factor in inflammatory cell function.

Objectives: We sought to determine whether increased cationic charge seen in an atopic microenvironment plays a role in the activation of eosinophils.

Methods: Human eosinophils were incubated with Sepharose beads coated with cationic or anionic compounds in the presence and absence of a cytokine cocktail (IL-3, IL-5, and GM-CSF) to simulate the milieu of inflammation. Eosinophil peroxidase and eosinophil-derived neurotoxin (EDN) release were compared with eosinophil morphology and expression of CD18, as determined by means of confocal microscopy.

Results: Cytokines with positively charged beads caused greater eosinophil peroxidase release (lysine coated, 44.2 nmol/L; compound 48/80, 40.0 nmol/L; or EDN coated, 49.1 nmol/L) than cytokines alone (14.9 nmol/L). Beads coated with heparin, dextran sulfate, and aspartic acid did not show this effect. EDN release was also induced by lysine-coated beads with cytokines (67.1 ng/100 microL) and blocked by heparin. Eosinophil incubation with wortmannin, genistein, and the src kinase inhibitor PP1 blocked cationic signaling. Eosinophils adherent to cationic-charged beads but not anionic-charged beads show polarization of CD18 expression toward the bead's surface.

Conclusion: Cationic-charged surfaces induce increased eosinophil mediator release by increasing the density of CD18 expression available at the target surface.