Regulation of alveolar macrophage p40phox: hierarchy of activating kinases and their inhibition by PGE2.

摘要: PGE2, produced in the lung during infection with microbes such as Klebsiella pneumoniae, inhibits alveolar macrophage (AM) antimicrobial functions by preventing H2O2 production NADPH oxidase (NADPHox). Activation of NADPHox complex is poorly understood AMs, although neutrophils it known to be mediated kinases including PI3K/Akt, protein kinase C (PKC) δ, p21-activated (PAK), casein 2 (CK2), and MAPKs. The p40phox cytosolic subunit has been recently recognized function a carrier for other subunits positive regulator activation, role previously considered unique another subunit, p47phox. regulation remains understood, effect PGE2 on its activation completely undefined. We addressed these issues rat AMs activated IgG-opsonized K. pneumoniae. kinetics consequences inhibition silencing revealed critical PKCδ-PAK-class I PI3K/Akt1 cascade upon bacterial challenge AMs; PKCα, ERK, CK2 were not involved. inhibited p40phox, effects A type II, independent interactions anchoring proteins, directed at distal class step. Defining that control AM are targets provides new insights into immunoregulation infected lung.