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Old Drug Holds Promise Against Opportunistic Lung Bug
Date:8/19/2010

d," said first author Jing Wang, Ph.D., research assistant professor in Pediatrics. "Since we reduced the response of the immune system, you would think the mice would get sicker. But instead, the mice treated with sulfasalazine were healthier. At first we thought it was due solely to the anti-inflammatory activity of the compound, but it turns out that sulfasalazine actually results in a reduced fungal burden. The drug helps the body clear the infection.

"We initially thought we had done something wrong, and so we repeated the experiment again and again. Then, when new technology was developed, we were able to document that the body cleared the infection more readily with sulfasalazine," added Wang.

Scientists have long known that the body's immune T cells are central to the body's response to fight off the infection. The Rochester team showed that the body's T cells spur macrophages to attack the fungus – to engulf its particles and chew them up in a process known as phagocytosis.

While scientists have long suspected that role for macrophages, the Rochester team relied on a new technology to gather the first direct evidence of macrophages engulfing fungal particles. The scientists worked closely with Timothy Bushnell, Ph.D., and others at Rochester's Flow Cytometry Resources Core, investigating new ways to use lasers to capture images of molecular events. Bushnell's team ultimately connected the team with scientists at Amnis. Together the group developed a new way to capture macrophage phagocytosis in single cells from mice infected with Pneumocystis. The technology enabled the team to capture more than 40,000 such events, compared to just a handful when using conventional microscopy.

The team showed that as macrophage activity increased, the animals' health improved and levels of fungus decreased. For example, 17 days after infection, mice treated with sulfasalazine had nine times as many macrophages that ha
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SOURCE University of Rochester Medical Center
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