INHIBITORY EFFECT OD PORCINE SURFACTANT ON THE RESPIRATORY BURST OXIDASE IN HUMAN NEUTROPHILS - ATTENUATION OF P47(PHOX) AND P67(PHOX) MEMBRANE TRANSLOCATION AS THE MECHANISM

Citation
W. Chao et al., INHIBITORY EFFECT OD PORCINE SURFACTANT ON THE RESPIRATORY BURST OXIDASE IN HUMAN NEUTROPHILS - ATTENUATION OF P47(PHOX) AND P67(PHOX) MEMBRANE TRANSLOCATION AS THE MECHANISM, The Journal of clinical investigation, 96(6), 1995, pp. 2654-2660
Citations number
51
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
96
Issue
6
Year of publication
1995
Pages
2654 - 2660
Database
ISI
SICI code
0021-9738(1995)96:6<2654:IEOPSO>2.0.ZU;2-R
Abstract
Surfactant has been shown to inhibit the production of reactive oxygen intermediates by various cells including alveolar macrophages and per ipheral blood neutrophils, Superoxide (O-2(-)) production by the respi ratory burst oxidase in isolated plasma membranes prepared from PMA-tr eated human neutrophils was significantly attenuated by prior treatmen t with native porcine surfactant, The effect was concentration depende nt with half-maximal inhibition seen at approximate to 0.050 mg surfac tant phospholipid/ml, Kinetic analyses of the membrane-bound enzyme pr epared from neutrophils stimulated by PMA in the presence or absence o f surfactant demonstrated that surfactant treatment led to a decrease in the maximal velocity of O; production when NADPH was used as substr ate, but there was no effect on enzyme substrate affinity, Immunoblott ing studies demonstrated that surfactant treatment induced a decrease in the association of two oxidase components, p47(phox) and p67(phox), with the isolated plasma membrane. In contrast, surfactant treatment of the cells did not alter the phosphorylation of p47(phox). A mixture of phospholipids (phosphatidylcholine and phosphatidylglycerol in a 7 :3 ratio) showed similar inhibition of the PMA-induced O-2(-) generati on. Taken together, these data suggest the mechanism of surfactant-ind uced inhibition of O-2(-) production by human neutrophils involves att enuation of translocation of cytosolic components of the respiratory b urst oxidase to the plasma membrane. The phospholipid components of su rfactant appear to play a significant role in this mechanism.