Eosinophil superoxide anion generation induced by adhesion molecules and leukotriene D4.
BACKGROUND
Eosinophils preferentially accumulate at sites of inflammation in the asthmatic airway. Participation of circulating eosinophils in the airway inflammation in asthma involves their interaction with adhesion molecules expressed on the endothelial cell surface and exposure to inflammatory mediators, such as cysteinyl leukotrienes (cysLTs).


OBJECTIVE
To investigate whether interaction of eosinophils with adhesion molecules modifies the functions of these cells induced by cysLTs.


METHODS
Eosinophils were isolated from the blood of healthy donors, incubated in the EIA plates coated with adhesion proteins, and then exposed to LTD4. The generation of superoxide anion (O2-), adhesion to the plates, and release of eosinophil-derived neutrotoxin (EDN) were evaluated.


RESULTS
Neither VCAM-1 nor LTD4 (100 nM) independently induced eosinophil O2- generation, however, combined exposure to the two molecules synergistically induced eosinophil O2- generation. ICAM-1 by itself induced eosinophil O2- generation, which was enhanced by LTD4. On the contrary, P-selectin did not induce O2- generation, either in the presence or absence of LTD4. LTD4 significantly enhanced eosinophil adhesion to rh-VCAM-1 and rh-ICAM-1, but not to rh-P-selectin. Finally, we observed that combined exposure of eosinophils to LTD4 and VCAM-1 induced the release of EDN.


CONCLUSIONS
Combined exposure to VCAM-1 or ICAM-1 and cysLT effectively induces the effector functions of eosinophils. Eosinophil adhesion to and migration across endothelial cells via these specific adhesion proteins and subsequent exposure to cysLTs may be mechanisms underlying activation of the effector functions of eosinophils in the asthmatic airway.
Mori
Mariko
M
Department of Respiratory Medicine, Saitama Medical University, Saitama 350-0495, Japan.
Takaku
Yotaro
Y
Kobayashi
Takehito
T
Hagiwara
Koichi
K
Kanazawa
Minoru
M
Nagata
Makoto
M
D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D047208:Eosinophil-Derived Neurotoxin / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism* / Q000494:pharmacology; D017998:Leukotriene D4 / Q000378:metabolism* / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism* / Q000494:pharmacology
D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D017998:Leukotriene D4; D047208:Eosinophil-Derived Neurotoxin