Researchers uncover how the inhaled form of anthrax disarms bacteria-fighting white blood cells before they can fend off the disease

Sep 6 2005

University of Florida researchers have uncovered how the inhaled form of anthrax disarms bacteria-fighting white blood cells before they can fend off the disease, which kills most victims within days.

The lethal toxin in anthrax paralyzes neutrophils, the white blood cells that act as the body's first defense against infection, by impairing how they build tiny filaments that allow them to crawl throughout the body and eat invading bacteria.

Just two hours of exposure to the lethal toxin blocks the neutrophils' ability to produce these filaments by nearly 60 percent, paralyzing them and allowing the anthrax to move freely in the body, according to research released last week in The Journal of Infectious Diseases.

The need to find new ways to treat victims of bioterrorism has increased since the Sept. 11, 2001, terrorist attacks and the anthrax attacks that killed five people exposed to inhalation anthrax through the mail. The UF findings could lead to treatments that block anthrax from paralyzing the much-needed neutrophils, said Dr. Frederick Southwick, division chief of infectious diseases at the UF College of Medicine and the lead author of the paper.

"If your neutrophils work normally, you might be able to shut down this infection," said Southwick, who worked on the study with a team of UF researchers and investigators from the Centers for Disease Control and Prevention and Emory University. "The overall goal is to understand how anthrax toxins paralyze the immune system."

Researchers first noticed anthrax's effect on these white blood cells while reviewing the cases in the 2001 anthrax attacks.

The victims did not have elevated white blood cell counts, typical for most infections, and a large number of the inhaled anthrax bacteria had spread from the lungs into the bloodstream, which is unusual, Southwick said.

This led researchers to believe anthrax may be impairing the cells' ability to move and fight off the offending bacteria, an idea that had only been studied once before years earlier.

Using blood samples from volunteers, the researchers studied how neutrophils reacted when exposed to a purified form of anthrax lethal toxin, the part of the spore linked to the illness.

Unlike an intact inhalation anthrax spore, the pure toxin is not dangerous for researchers to use and allows them to isolate specifically how the toxin is affecting cells, Southwick said.

Low doses of the lethal toxin stopped the protein actin from building filaments to steer the neutrophils, stopping the body's immune response, the study found.

"Neutrophils crawl around in the body and roll around in the blood vessels and whenever they sense bacteria, they gobble it up like Pac-Man," said Russell During, a graduate student in the Interdisciplinary Program in Biomedical Sciences who worked with Southwick on the study. "If neutrophils are the first responders and they never get there, you're fighting a losing battle."

And inhalation anthrax works fast, which is one of the reasons why it is usually fatal, according to the CDC. The disease can be treated with antibiotics, but people often don't seek treatment until it is too late, said Philip C. Hanna, an associate professor of microbiology and immunology at the University of Michigan Medical School.

"A person can die before they know they are terribly sick at all," Hanna said.

Symptoms of inhalation anthrax resemble the common cold and progress to breathing problems, shock and often death, according to the CDC.

But in the 2001 attacks, only half the 10 people who contracted inhalation anthrax died. The five other victims were diagnosed and treated earlier due to quick communication from the doctors who pinpointed the first anthrax infection, Southwick said.

Twelve other people contracted cutaneous (skin) anthrax infections, which are not usually fatal.

Knowledge about anthrax and how it works has improved since then, too, Hanna said. Now doctors know what anthrax looks like and what public health steps to take, he added.

The next step for UF researchers is to pinpoint the exact protein the lethal toxin is targeting in the neutrophil. There are more than 100 proteins that regulate actin-filament formation, and researchers have already isolated one that may be responsible, Southwick said.

The UF findings also could affect research on other diseases. Because actin is found in every cell, the study could lead researchers to know more about how tumors and other cells move in the body, Southwick said.

"It relates to wound healing, it may relate to many diseases and many problems," he said.