ACTIVATION OF THE RESPIRATORY BURST OXIDASE

The respiratory burst oxidase of phagocytes and B lymphocytes catalyzes the reduction of oxygen by NADPH to form O-2(.-), the precursor of a group or reactive oxidants that are employed by phagocytes as microbicidal agents. The enzyme is active in stimulated cells but dormant in resting cells. it is composed of several subunits: p22(phox), gp91(phox), p47(phox), p67(phox), and a low molecular weight guanine nucleotide-binding protein. The components p22(phox) and gp91(phox) form cytochrome b(558), a flavohemoprotein that resides in the cortical cytoskeleton and in the membranes of the specific granules. The other components are found in the cytosol of resting cells, but migrate to the cortical cytoskeleton when the neutrophils are activated, where they assemble the active oxidase. Migration to the cortical cytoskeleton is caused in part by the appearance of a membrane binding site on one or more of the cytosolic subunits, possibly due to the phosphorylation of p47(phox) that takes place during cell activation.