When the macrophage engulfs a foreign body such as a bacterium, a parasite or another potential pathogen, an enzyme called NAD(P)H oxidase in the plasma membrane of the macrophage is activated . This enzymes transfers reducing equivalents from NAD(P)H to molecular oxygen leading to the formation of extremely reactive superoxide and hydroxyl radicals (
and OH· ) according to the following reactions:
As intermediates of the reaction are formed the radicals
and OH· . Formation of these radicals occurs locally
at the place of engulfment allowing the active oxygen species to
react with the phospholipids of the pathogen's membrane which then
becomes permeabilized. Radicals also react with the pathogen's
macromolecules such as DNA by introducing strand breaks.Following the fusion of the phagosome with the endosomal compartment of the cell an acidification of this compartment, by the action of a proton ATPase in its membrane, leads to a significant drop in pH (pH 5). As a result proteins start to denature and unfold which renders them accessible to hydrolases.
Fusion of the endosomal compartment with primary lysosomes, forming the phagolysosomal compartment, then leads to release of acid hydrolases (digestive enzymes) into this compartment. Macromolecules such as DNA, RNA, proteins and carbohydrates are now degraded and the pathogen digested.