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 (O 2 − ) 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 B 4 (LTB 4 ). O 2 − 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 O 2 − generation from eosinophils. In contrast, the potency of eotaxin or LTB 4 for these functions was much less. PAF and C5a also significantly enhanced eosinophil adhesion, whereas eotaxin and LTB 4 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 > LTB 4 . Conclusions The potency of PAF and C5a for inducing effector function in eosinophils was greater than that of eotaxin or LTB 4 . 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.