Alkalization of the phagosomal lumen by NOX2

Stable Identifier
Reaction [transition]
Homo sapiens
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After the fusion of phagosome and lysosome lumen acidity rises and the activity of lysosomal proteases increases, conferring proteolytic ability. However antigens must be spared from complete proteolytic destruction. Dendritic cells (DCs) achieve this by regulating the level of proteolysis and phagosomal acidification. DCs recruit the NADPH oxidase NOX2 to the phagosome and mediate sustained production of low levels of reactive oxygen species (ROS), causing active alkalization of the phagosomal lumen (Savina et al. 2006, Ramachandra et al. 2009). NOX2 consumes oxygen and protons (pumped by V-ATPase or other H+ voltage-gated channels) to produce ROS and this lowers phagosome acidity. This apparently reduces antigen proteolysis to a level that allows processing but does not fully destroy the antigenic peptides, favouring increased MHC-I cross presentation (Ramachandra et al. 2009). Rab27a controls the recruitment of NOX2 to DC phagosomes (Savina et al. 2007).
Literature References
PubMed ID Title Journal Year
20171863 Intracellular mechanisms of antigen cross presentation in dendritic cells

Savina, A, Amigorena, S

Curr Opin Immunol 2010
19217269 MHC molecules and microbial antigen processing in phagosomes

Simmons, D, Harding, CV, Ramachandra, L

Curr Opin Immunol 2009
17351642 Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes

Tolmachova, T, Seabra, MC, Pascolo, S, Dang, PM, Wasmeier, C, Jancic, C, Savina, A, Amigorena, S, Gougerot-Pocidalo, MA, El-Benna, J, Raposo, G

Nat Cell Biol 2007
8089108 The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation. Phosphorylation of sites recognized by protein kinase C and by proline-directed kinases

Faust, LP, el Benna, J, Babior, BM

J Biol Chem 1994
9804763 p40(phox) is phosphorylated on threonine 154 and serine 315 during activation of the phagocyte NADPH oxidase. Implication of a protein kinase c-type kinase in the phosphorylation process

Fuchs, A, Bouin, AP, Vignais, PV, Grandvaux, N

J. Biol. Chem. 1998
18682599 NADPH oxidase controls phagosomal pH and antigen cross-presentation in human dendritic cells

Geffner, J, Vermeulen, M, Hermine, O, Rosenzweig, SD, Perez, L, Savina, A, Amigorena, S, Mantegazza, AR, Faure, F

Blood 2008
Catalyst Activity

superoxide-generating NAD(P)H oxidase activity of NOX2 complex [phagocytic vesicle membrane]

Orthologous Events
Cross References
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