Out Phoxing the Endothelium

The importance of the contribution from Li et al1 presented in this issue lies as much in the questions it raises as in those it answers. In setting out to prove that p47phox, a regulatory subunit of the phagocyte NADPH oxidase, is equally vital to the superoxide-generating enzyme of vascular endothelial cells, which they successfully did, they also turned up a number of unexpected observations. The latter results, whose interpretation will necessarily remain speculative for the time being, may become fertile ground for future investigations, not only of the endothelium, but also of other tissues that express variants of this enzyme complex first characterized in phagocytes.In the neutrophil, the bactericidal oxidative burst results from massive superoxide anion production by an NADPH oxidase, a complex of 5 major subunits, the membrane bound gp91phox and p22phox, and the regulatory cytosolic components p47phox, p67phox, and Rac.2 The importance of p47phox is well documented because its phosphorylation appears to be the limiting step required for assembly of the active enzyme complex.2 Furthermore, mutations in p47phox are a cause of chronic granulomatous disease, an immune deficiency resulting from impaired phagocyte activity.It is now clear that many other tissues, including all layers of the vascular wall, also produce superoxide and its derivatives.3 These reactive oxygen species are no longer regarded simply as undesirable by-products of aerobic metabolism but also as essential second messengers …