UW professor of medicine Seymour Klebanoff was the first to discover a key biochemical mechanism used by the immune system to destroy invading microorganisms.

The body fights off invaders like bacteria by unleashing types of white blood cells called "phagocytes." The phagocytes engulf the bacterial cells and sequester them in an intracellular compartment called the phagosome. During that process, phagocytes consume oxygen at a sharply increased rate in what is called a "respiratory burst." The burst generates hydrogen peroxide along with highly reactive chemicals called free radicals (an atom or group of atoms with an unpaired electron). Meanwhile, granules inside the phagocyte release an arsenal of enzymes and toxic agents, including a bright green enzyme found in pus called yeloperoxidase, into the phagosome.
Myeloperoxidase in turn reacts with the hydrogen peroxide and an ion such as chloride (a component of table salt, ubiquitous in the body), generating a powerful weapon against bacteria: hypochlorous acid--the active ingredient in household bleach. Klebanoff first described this "myeloperoxidase-mediated antimicrobial system" in a paper published in 1967 in The Journal of Experimental Medicine.
"It's as if the phagocytes attract bacteria into an intracellular swimming pool and then turn on a spigot of Clorox to kill them," says Klebanoff. Infants born with a genetic defect that impairs the respiratory burst of their white blood cells face a lower life expectancy. Klebanoff and others have had some success in treating these patients with gamma interferon to kick-start their inactive phagocytes.
This vital weaponry that protects us against microorganisms can also damage other kinds of cells and organs. Klebanoff and colleagues showed the system can cause damage to the kidney, sperm cells, red and white blood cells, platelets, and tumor cells.
Recently, Klebanoff demonstrated that hydrogen peroxide formed by bacteria called lactobacilli can kill the HIV virus. Those bacteria are the predominant bacterial species found in the vagina of normal women. But hydrogen peroxide can also activate the part of the AIDS virus that functions as an on-off switch for viral replication. Klebanoff says that at this point it's not clear which, if either, of the two diametrically opposed roles these bacteria play: killing the virus or activating viral replication. But he emphasizes that these bacteria are of considerable interest not only with respect to heterosexual AIDS transmission, but in other sexually transmitted diseases and vaginal infections as well.
Authored by Javed Sheikh, MD, Instructor, Department of Medicine, Division of Allergy and Inflammation, Harvard Medical School

INTRODUCTION Section 2 of 10
Background: Myeloperoxidase (MPO) is a human enzyme in the azurophilic granules of neutrophils and in the lysosomes of monocytes. Its major role is to aid in microbial killing. Although MPO received little clinical attention until 1966, the enzyme was first isolated in 1941, and deficiency of MPO was first described in 1954. Some patients with MPO deficiency have impaired microbial killing, but most are asymptomatic, and the condition usually goes undiagnosed. Since most cases go undiagnosed, the condition initially was believed to be very rare; only 15 cases were reported before the 1970s. Modern laboratory techniques have allowed us to discover that MPO deficiency actually is not so rare.

Normal function of myeloperoxidase MPO, an iron-containing protein, is found in the azurophilic granules of neutrophilic polymorphonuclear leukocytes (PMNs) and in the lysosomes of monocytes in humans. MPO is most abundant in the granules of neutrophils. Monocytes contain only about a third of the MPO present in neutrophils. When neutrophils become activated, which can happen in conjunction with phagocytosis, they undergo a process referred to as a respiratory burst. This respiratory burst causes production of superoxide, hydrogen peroxide, and other reactive oxygen derivatives, which are all toxic to microbes. During respiratory bursts, granule contents are released into the phagolysosomes and outside the cell, allowing released contents to come into contact with any microbes present. MPO catalyzes the conversion of hydrogen peroxide and chloride ions (Cl) into hypochlorous acid. Hypochlorous acid is 50 times more potent in killing than hydrogen peroxide.

MPO also chlorinates phagocytosed bacteria directly, so the MPO-hydrogen peroxide-Cl system seems to have an important role in microbial killing. While the exact mechanism by which microbial killing occurs is controversial, it is fairly certain that the MPO system is important for the process to occur optimally. In addition to killing bacteria, the products of the MPO-hydrogen peroxide-Cl system are thought to play a role in killing fungi, parasites, protozoa, viruses, tumor cells, natural killer (NK) cells, red cells, and platelets.