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.

• Authors: Darryl J Adamko, Yingqi Wu, Farnam Ajamian, Ramses Ilarraza, Redwan Moqbel, Gerald J Gleich
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 122 Issue 2 Pg. 383-90, 390.e1-4 (Aug 2008) ISSN: 1097-6825 [Electronic] United States
• PMID: 18455220 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• CD18 Antigens
• Cations
• Cytokines
• Protein Kinase Inhibitors
• Receptors, Neuropeptide Y
• Stilbenes
• neuropeptide Y4 receptor
• 3,3',4,5'-tetrahydroxystilbene
• Heparin
• Dextran Sulfate
• Genistein
• Eosinophil Peroxidase
• Protein Kinases
• Eosinophil-Derived Neurotoxin
• Eosinophil Cationic Protein
• Wortmannin

Topics

• Androstadienes (pharmacology)
• CD18 Antigens (metabolism)
• Cations
• Cell Adhesion
• Cell Degranulation
• Cell Polarity
• Cytokines (immunology)
• Dextran Sulfate (pharmacology)
• Eosinophil Cationic Protein (metabolism)
• Eosinophil Peroxidase (metabolism)
• Eosinophil-Derived Neurotoxin (metabolism)
• Eosinophils (drug effects, immunology, metabolism)
• Genistein (pharmacology)
• Heparin (pharmacology)
• Humans
• Protein Kinase Inhibitors (pharmacology)
• Protein Kinases (metabolism)
• Receptors, Neuropeptide Y (metabolism)
• Signal Transduction
• Stilbenes (pharmacology)
• Wortmannin