Diagnostic assays for myeloperoxidase and myeloperoxidase deficiency

Neutrophils (PMN) represent the dominant cell in the acute response to microbial infection and can contribute to some of the tissue damage that accompanies sterile inflammation. Effective antimicrobial activity in neutrophil phagosomes reflects the combined action of soluble agents in plasma with PMN-derived reactive oxygen species and granule proteins, including the azurophilic granule protein myeloperoxidase (MPO). The inhibition or the absence of the MPO-H2O2-halide system results in marked reduction in PMN killing of a variety of microbes, implicating its relative prominence in the hierarchy of PMN antimicrobial systems. Although the most profound clinical defects are manifested in patients lacking the capacity to generate reactive oxygen species, as seen in chronic granulomatous disease, an inherited deficiency of MPO can also increase the frequency or the severity of clinical infections.Like related peroxidases expressed in animals, MPO can catalyze both one- and two-electron oxidations, thereby mediating peroxidation and halogenation, respectively. The presence of each activity can be assessed in inflammatory fluids or by stimulated PMN. Furthermore, histochemical staining provides an assessment of functional MPO in tissue or within PMN, and immunoblotting of isolated PMN for MPO can provide additional insight into the molecular basis of the observed absence of functional enzyme.