Klebanoff to present Distinguished Scientist Lecture

Seymour Klebanoff

While lounging in a cool swimming pool on a hot day this summer, imagine yourself as a microorganism recently engulfed by a phagocyte. You'll be closer than you think.

When these immune system cells ingest invading microorganisms, they surround them with fluid-filled sacs called phagosomes. The phagocytes discharge an enzyme, myeloperoxidase, into these intracellular pools that reacts with hydrogen peroxide (H2O2) formed by the stimulated phagocytes. Together, the two oxidize a third component, chloride, to form a very powerful oxidant called hypochlorous acid — the same oxidant, in fact, used to sanitize your average swimming pool.

Still feel like lolling in the water? No worries. Commercial hypochlorous acid is mercifully diluted. In the phagosome, however, this powerful oxidant can kill almost any bacteria.

Oxidants are highly unstable molecules that attract electrons. When they come within the vicinity of a microorganism, as they do in the phagosome, they literally steal electrons from the enemy, making it impossible for the microorganism to replicate.

These chemical reactions among oxidants in the cell are part of a process called phagocytosis, which Dr. Seymour Klebanoff, professor of medicine, will discuss in more detail in the Distinguished Scientist Science in Medicine lecture on Friday, June 5, from noon to 1 p.m. in room T-625 of the Health Science Center. His lecture is titled “Oxidants, Modulins and Host Defense.”

Klebanoff, a world leader and pioneer in the field, was in fact the first to show that phagocytes use these components — H2O2, myeloperoxidase and chloride — to form the oxidant that kills ingested microorganisms. In later work, he showed that this murderous intracellular oxidant does not always work to our benefit, however.

“It's a double-edged sword because these same oxidants can be released outside the cell and damage surrounding tissue and contribute to the pathogenesis of disease,” he said. Under some circumstances, there is evidence that the phenomenon may damage kidney tissue, Klebanoff said.

Klebanoff's research has also led to the discovery that bacteria found in the vaginal flora called lactobacilli also produce H2O2 and use it to kill other bacteria in the region. Studies show that women who have a low level of lactobacilli may have an overgrowth of other harmful bacteria.

Additionally, Klebanoff proved that oxidants released by phagocytes and lactobacilli can be toxic to HIV, the virus that causes AIDS. Yet, again, here is that double-edged sword. While it is toxic to the HIV virus, H2O2 discharged by lactobacilli can also activate HIV's “long terminal repeat” (LTR) — the name for portions of the viral genome containing the sequences that allow the virus to replicate.

More recent research has shown that lactobacilli and another bacteria, staphylococci, release compounds unrelated to H2O2 called modulins that result in septic shock, which has fever-like symptoms and can make us seriously ill. When we're attacked by staphylococci, these modulins induce an increase in the synthesis and release of cytokines, soluble molecules that control many reactions between cells. Research suggests that cytokines may affect the area of our brain that regulates temperature, Klebanoff said.

Klebanoff's laboratory has determined the molecular structure of three polypeptides that may be responsible for inducing the synthesis of cytokines. “By neutralizing these agents, we hope to prevent some forms of septic shock,” he said.

Klebanoff has been a faculty member at the UW since 1962. From 1976 to 1994, he was head of the Division of Allergy and Infectious Diseases in the Department of Medicine. His past awards include the Bristol-Meyers Squibb Award for Distinguished Achievement in Infectious Disease Research. He is a member of the National Academy of Sciences and Institute of Medicine.

This spring, Klebanoff became a fellow of the American Academy of Arts and Sciences. ¶

Will Morton