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Sep 14, 2007

Platelets Implicated in the Fight against Inflammation

  • Platelets help neutrophils fight inflammation, report researchers from Charite and the Max Delbrueck Center for Molecular Medicine. “We found an entirely new mechanism by which neutrophils induce inflammation,” says Ralph Kettritz, M.D., professor of medicine at the Medical Faculty of Charite and investigator at the Max Delbrueck Center for Molecular Medicine.

    “So far, scientists have shown that platelets form clots and neutrophils can cause symptoms of inflammation such as swelling, redness, and heat. In this study, we show that platelets and neutrophils sometimes work together to heal a wound or fight an infection.”

    In addition to neutrophils, macrophages and lymphocytes also engage in the fight against bacteria. These cells are activated by tumor necrosis factor (TNF) released by the neutrophils.

    Although there are several ways by which neutrophils release TNF, the investigators report that they found a totally new and different way that neutrophils can be stimulated to produce TNF. “We found that a neutrophil can acquire receptors that are not already present on its surface and use them to stimulate the production of TNF,” says Dr. Kettritz.

    The receptors, called GPIIb/IIIa, are sent to neutrophils by platelets. These receptors are packaged in vesicles called microparticles that, when they reach a neutrophil, bind to its surface and release the receptors. The receptors are then incorporated into the neutrophil’s cell membrane.

    Dr. Kettritz and his team also found that these newly-acquired receptors did not work alone. To stimulate neutrophils to produce TNF, the GPIIb/IIIa receptor works in tandem with the receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF). The GM-CSF substance are already known to be released at the early stages of inflammation.

    The scientists found that the neutrophil produces TNF both when GPIIb/IIIa binds to a protein outside the cell called fibronectin and when the GM-CSF receptor binds to GM-CSF. “We also found for the first time that receptors involved in blood clotting also trigger an inflammatory response,” Dr. Kettritz notes.

    Kettritz and colleagues tested three drugs currently used to prevent blood clotting by inhibiting GPIIb/IIIa receptors—abciximab, epifibatide, and tirofiban—on cell cultures in which neutrophils had received the GPIIb/IIIa receptors from platelets and confirmed the drugs’ effects on inflammation. The scientists showed that all three drugs inhibited the production of TNF, which reduced inflammation in these cells.

    These results also led the researchers to speculate that some of the beneficial effects of the three drugs on patients with acute coronary syndrome result from their anti-inflammatory properties.

    The study will be published in the September 21 issue of the Journal of Biological Chemistry.



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