Eosinophils play a primary role in the pathophysiology of @entity565 . In the lung, the activation state of the infiltrating eosinophils determines the extent of tissue damage. @entity225 ( @entity225 ) and leukotriene B4 (LTB4) are important signaling molecules involved in eosinophil recruitment and activation. However, the physiological processes that regulate these activation events are largely unknown. In this study we have examined the mechanisms of @entity1 eosinophil @entity1110 oxidase regulation by @entity225 , LTB4, and @entity4621 ( @entity4515 ). These stimuli activate a @entity8862 -sensitive plasma membrane proton channel, and treatment of eosinophils with @entity8862 blocks @entity224 production. We have demonstrated that eosinophil intracellular pH is not altered by @entity225 activation of @entity1110 oxidase. Additionally, @entity4456 inhibitors block @entity4515 , @entity225 and LTB4 mediated @entity224 formation. Interestingly, the @entity4456 -selective inhibitor, @entity12703 , does not block proton channel activation by @entity4515 indicating that the oxidase and the proton conductance are regulated at distinct phosphorylation sites. @entity225 and LTB4, but not @entity4515 , stimulated @entity224 production is also blocked by inhibitors of PI 3-kinase indicating that activation of this enzyme is an upstream event common to both receptor signaling pathways. Our results indicate that the G-protein-coupled LTB4 receptor and the @entity225 cytokine receptor converge on a common signaling pathway involving PI 3-kinase and @entity4456 to regulate @entity1110 oxidase activity in @entity1 eosinophils.

Regulation of @entity1 eosinophil XXXX oxidase activity: a central role for @entity4456 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity8862 :: ('CHEBI:37256', 'Chemical') :: ['Zn2+'] @entity225 :: ('3567', 'Gene') :: ['Interleukin-5', 'IL-5'] @entity565 :: ('MESH:D001249', 'Disease') :: ['asthma'] @entity12703 :: ('MESH:C085746', 'Chemical') :: ['rottlerin'] @entity4515 :: ('CHEBI:60755', 'Chemical') :: ['PMA'] @entity1110 :: ('MESH:D009249', 'Chemical') :: ['NADPH'] @entity4621 :: ('CHEBI:37532', 'Chemical') :: ['phorbol ester'] @entity4456 :: ('5580', 'Gene') :: ['PKCdelta'] @entity224 :: ('MESH:D013481', 'Chemical') :: ['superoxide']
@entity1110 :: (MESH:D009249,Chemical) :: ['NADPH']
