Reactome | Alkalization of the phagosomal lumen by NOX2

Alkalization of the phagosomal lumen by NOX2

Stable Identifier

R-HSA-1236967

Type

Reaction [transition]

Species

Homo sapiens

Compartment

phagolysosome, cytosol

ReviewStatus

5/5

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Alkalization of the phagosomal lumen by NOX2

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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