GAINESVILLE, Fla. - University of Florida researchers have uncoveredhow the inhaled form of anthrax disarms bacteria-fighting white bloodcells before they can fend off the disease, which kills most victimswithin days.
The lethal toxin in anthrax paralyzes neutrophils, the white bloodcells that act as the body's first defense against infection, byimpairing how they build tiny filaments that allow them to crawlthroughout the body and eat invading bacteria.
Just two hours of exposure to the lethal toxin blocks theneutrophils' ability to produce these filaments by nearly 60 percent,paralyzing themand allowing the anthrax to move freely in the body, according toresearch released last week in The Journal of Infectious Diseases.
The need to find new ways to treat victims of bioterrorism hasincreased since the Sept. 11, 2001, terrorist attacks and the anthraxattacks that killed five people exposed to inhalation anthrax throughthe mail. The UF findings could lead to treatments that block anthraxfrom paralyzing the much-needed neutrophils, said Dr. FrederickSouthwick, division chief of infectious diseases at the UF College ofMedicine and the lead author of the paper.
"If your neutrophils work normally, you might be able to shutdown thisinfection," said Southwick, who worked on the study with a team of UFresearchers and investigators from the Centers for Disease Control andPrevention and Emory University. "The overall goal is to understand howanthrax 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 anthraxbacteria had spread from the lungs into the bloodstream, which isunusual, Southwick said.
This led researchers to believe anthrax may be impairing thecells' ability to move and fight off the offending bacteria, an ideathat hadonly been studied once before years earlier.
Using blood samples from volunteers, the researchers studiedhow neutrophils reacted when exposed to a purified form of anthraxlethal toxin, the part of the spore linked to the illness.
Unlike an intact inhalation anthrax spore, the pure toxin isnot dangerous for researchers to use and allows them to isolatespecifically how the toxin is affecting cells, Southwick said.
Low doses of the lethal toxin stopped the protein actin frombuilding filaments to steer the neutrophils, stopping the body's immuneresponse, the study found.
"Neutrophils crawl around in the body and roll around in the bloodvessels and whenever they sense bacteria, they gobble it up likePac-Man," said Russell During, a graduate student in the Interdisciplinary Program in Biomedical Sciences who worked withSouthwick 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 reasonswhy it is usually fatal, according to the CDC. The disease can betreated with antibiotics, but people often don't seek treatment untilit is too late,said Philip C. Hanna, an associate professor of microbiology andimmunology 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 andprogress to breathing problems, shock and often death, according to theCDC.
But in the 2001 attacks, only half the 10 people who contractedinhalation anthrax died. The five other victims were diagnosed andtreated earlier due to quick communication from the doctors whopinpointed 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 sincethen, too, Hanna said. Now doctors know what anthrax looks like andwhat publichealth steps to take, he added.
The next step for UF researchers is to pinpoint the exact protein thelethal toxin is targeting in the neutrophil. There are more than 100proteins that regulate actin-filament formation, and researchers havealready isolated one that may be responsible, Southwick said.
The UF findings also could affect research on other diseases. Becauseactin is found in every cell, the study could lead researchers to knowmore about how tumors and other cells move in the body, Southwick said.
"It relates to wound healing, it may relate to many diseases and manyproblems," he said.
Cite This Page: