چکیده (انگلیسی):

Background: Eosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins,
complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression
of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated
through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice
exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these
danger signals remains insufficiently understood.
Methods: We examined migration, adhesion, superoxide production and degranulation of human eosinophils.
Isolated eosinophils were incubated with monosodium urate (MSU) crystals and ATPgS, a nonhydrolysable
ATP analogue. To determine the involvement of P2 or P2Y2 receptors in eosinophil responses
to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP
(oATP), or anti-P2Y2 antibody before incubation with MSU crystals or ATPgS.
Results: MSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced
production of superoxide. oATP abolished eosinophil responses to MSU crystals, suggesting involvement
of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATPgS, induced migration of eosinophils
through a model basement membrane, adhesion to rh-ICAM-1, superoxide generation, and
degranulation of eosinophil-derived neurotoxin (EDN). oATP and anti-P2Y2 significantly reduced these
eosinophil responses.
Conclusions: ATP serves as an essential mediator of functional responses in human eosinophils. Eosinophil
responses to ATP may be implicated in airway inflammation in patients with asthma.