Myeloperoxidase

Overview
Myeloperoxidase (MPO) is a peroxidase enzyme most abundantly present in neutrophil granulocytes (a subtype of white blood cells). It is a lysosomal protein stored in azurophilic granules of the neutrophil. MPO has a heme pigment, which causes its green color in secretions rich in neutrophils, such as pus and some forms of mucus.

Studies have demonstrated neutrophil activation as they pass through the coronary bed in patients with ACS. Furthermore, MPO levels have recently been shown to be an independent predictor of outcome in ACS.

Structure
The 150 kDa MPO protein is a dimer consisting of two 15 kDa light chains and two variable-weight glycosylated heavy chains bound to a prosthetic heme group. Three isoforms have been identified, differing only in the size of the heavy chains. It contains a calcium binding site with 7 ligands forming a pentagonal pyramid conformation. One of the ligands is the carbonyl group of Asp 96. Calcium binding is important for structure of the active site because of Asp 96's close proximity to the catalytic His95 side chain.

Function
MPO produces hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion (Cl-) during the neutrophil's respiratory burst. It requires heme as a cofactor. Furthermore, it oxidizes tyrosine to tyrosyl radical using hydrogen peroxide as oxidizing agent.

Hypochlorous acid and tyrosyl radical are cytotoxic, so they are used by the neutrophil to kill bacteria and other pathogens.

Genetics
The gene is located on chromosome 17 (17q23.1).

Role in disease
Myeloperoxidase deficiency is a hereditary deficiency of the enzyme, which predisposes to immune deficiency.

Antibodies against MPO have been implicated in various types of vasculitis, most prominently crescentic glomerulonephritis and Churg-Strauss syndrome. They are detected as perinuclear ANCAs (pANCAs), as opposed to the cytoplasmic ANCAs (cANCAs) against proteinase 3 (PR3), which are strongly associated with Wegener's granulomatosis.

Diagnostic use
Routine testing of MPO is not performed. A 2003 study suggested that it could serve as a sensitive predictor for myocardial infarction in patients presenting with chest pain. Currently, PrognostiX Inc., run out of the Cleveland Clinic in Cleveland, Ohio, is the only company to have an FDA approved ELISA test kit for MPO concentration. The product is known as CardioMPO and is used in clinical settings to triage patients that present chest pain. It operates using the sandwich ELISA method.

Historically, immunohistochemical staining for myeloperoxidase was used in the diagnosis of acute myeloid leukemia to demonstrate that the leukemic cells were derived from the myeloid lineage. However, more recently, the use of myeloperoxidase staining in this setting has been supplanted by the widespread use of flow cytometry. Myeloperoxidase staining is still important in the diagnosis of extramedullary leukemia, or chloroma.