To see the mast cells in action rather than in a culture dish, senior research scientist Mindy Tsai, DMSc, helped produce genetically engineered mast cells that could or could not respond normally to endothelin-1. The researchers could then selectively transplant these mast cells to mice that lacked the cells and thus see how it affected the ability to respond to endothelin-1 or bacterial infection.

Most of the mice without mast cells died as a result of bacterial infection. But survival during sepsis was greatly improved in the mice with mast cells that could respond normally to endothelin-1. The scientists found that endothelin-1 can activate mast cells in the mice and, once triggered, the cells produced another protein that breaks down endothelin-1, reducing its toxic effects. In other words, said Galli, the mast cells help to restore normal physiological balance in the mice with high levels of endothelin-1.

High levels of endothelin-1 have been reported in a number of human diseases, such as high blood pressure, pulmonary hypertension, asthma, congestive heart failure, renal failure and gastric ulcers, said Galli. Moreover, mast cells have been implicated in many of the same disorders.

"Although we have studied a bacterial infection as a kind of first test case, we hope to be able to develop models that would allow us to study this phenomenon in other diseases as well," he said. "We are too early in this work to see clearly what the therapeutic potential will be."

Other scientists have considered the possibility of eliminating mast cells as a possible treatment for diseases such as asthma. However, Galli said his team's results offer an example of a beneficial function that would be lost if those cells were eliminated.

"It's reassuring that evolution has produced cells that under some circumstances have significant benefit, even though when they are activated inappropriately,
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Contact: Mitzi Baker
mitzibaker@stanford.edu
650-725-2106
Stanford University Medical Center
14-Nov-2004