How White Cells Wage War

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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 myeloperoxidase, 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.footnote 1 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.footnote 2 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.

  1. "Klebanoff to receive Bristol-Myers Squibb Award for infectious disease research accomplishments," University Week, Nov. 30, 1995.
  2. "Bacteria May Influence Transmission of HIV," Medicine Northwest, Winter 1993.

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