Cellular adhesion is required for effector functions of human eosinophils via G-protein coupled receptors.
BACKGROUND
Eosinophils play an important role in the pathogenesis of allergic diseases. Chemoattractants, including platelet-activating factor (PAF) and complement component 5a (C5a), induce eosinophil infiltration and promote eosinophil effector functions.


OBJECTIVE
To compare eosinophil degranulation and superoxide anion (O2-) generation induced by various chemoattractants, and to elucidate the role of cellular adhesion on these effector functions.


METHODS
Human eosinophils were stimulated with PAF, C5a, eotaxin, or leukotriene B4 (LTB4). O2- generation was assayed by a chemiluminescence method using a Cypridina luciferin analog as the amplifier. Degranulation and adhesion were measured by quantitating eosinophil protein X by radioimmunoassay. Expression of CD11b on eosinophils was measured by flow cytometry.


RESULTS
PAF and C5a induced significant degranulation and O2- generation from eosinophils. In contrast, the potency of eotaxin or LTB4 for these functions was much less. PAF and C5a also significantly enhanced eosinophil adhesion, whereas eotaxin and LTB4 did not. CD11b expression on eosinophils was enhanced by all four stimulants, and the order of potency to induce CD11b expression was C5a > PAF > eotaxin > LTB4.


CONCLUSIONS
The potency of PAF and C5a for inducing effector function in eosinophils was greater than that of eotaxin or LTB4. The magnitude of the effector function was consistent with the degree of eosinophil adherence induced by each stimulant. These results suggest that effector functions of eosinophils which are mediated through G-protein coupled receptors are dependent on cellular adhesion.
Department of Pediatrics, Gunma University School of Medicine, Japan.
Toru
T
Fujiu
Masahiko
M
Kato
Hirokazu
H
Kimura
Atsushi
A
Tachibana
Masato
M
Suzuki
Yasushi
Y
Nako
Akihiro
A
Morikawa
D002448:Cell Adhesion; D015550:Cell Degranulation; D015936:Complement C5a / Q000494:pharmacology; D004804:Eosinophils / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000032:analysis; D010972:Platelet Activating Factor / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D015936:Complement C5a; D019204:GTP-Binding Proteins