Human eotaxin induces eosinophil-derived neurotoxin release from normal human eosinophils.
BACKGROUND
Eosinophil granule proteins deposition at the site of allergic inflammation contributes to the late-phase reaction of hypersensitivity diseases. In the present communication, we describe the effect of human eotaxin on normal human eosinophil exocytosis measured as degranulation of eosinophil-derived neurotoxin (EDN).


METHODS
Purified eosinophils were obtained from normal healthy volunteers with the CD16-negative procedure. Purified eosinophils were stimulated with various concentrations of eotaxin and the amount of EDN released was analysed by radioimmunoassay. Flow cytometry was used to examine the surface expression of adhesion molecules on eosinophils.


RESULTS
Eotaxin significantly induced EDN release in a dose-dependent manner. The potency of eotaxin in this effect was equal to that of RANTES, and comparable to that of platelet-activating factor. Eotaxin-induced EDN release was blocked by cytochalasin B in a dose-dependent manner. The surface expression of CD11a, CD11b, CD18 and VLA-4 adhesion molecules on normal human eosinophils were not modulated by eotaxin stimulation.


CONCLUSIONS
These results indicate that eotaxin may play an important role not only as a selective chemotaxin for the cell type but also as a secretagogue. Furthermore, they demonstrate a degranulation mechanism(s) involving cytoskeletal changes which is probably independent of the quantitative expression of adhesion molecules.
El-Shazly
A
A
Department of Otorhinolaryngology, School of Medicine, Kumamoto University, Kumamoto City, Japan.
Masuyama
K
K
Nakano
K
K
Eura
M
M
Samejima
Y
Y
Ishikawa
T
T
D018821:CD18 Antigens / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000628:therapy; D066298:In Vitro Techniques; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D012260:Ribonucleases; D015398:Signal Transduction
C515456:CCL11 protein, human; D018821:CD18 Antigens; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D011506:Proteins; D016201:Receptors, Lymphocyte Homing; D003571:Cytochalasin B; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases