Washington, Sept 14(ANI): Scientists have identified a new mechanism that may help fight inflammatory diseases.
It has been discovered for the first time that the platelets which are the cells needed for blood clotting, help white blood cells called neutrophils in fighting inflammation.

The finding was done by Ralph Kettritz, Professor of Medicine at the Medical Faculty of the Charite and investigator at the Max Delbrueck Center for Molecular Medicine, Berlin, Germany, and colleagues.

“We found an entirely new mechanism by which neutrophils induce inflammation,” Kettritz said.

“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,” he added.

The study could result in formation of new anti-inflammatory compounds, which are needed for the treatment of inflammatory vascular injury.

A protective reaction from the tissues following a wound or infection takes place during inflammation. Resulting in white blood cells attacking bacteria and platelets formed clots that can close any potential wound.

The first to launch an attack against the bacteria are the white blood cells called neutrophils. Through substances, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), that are released at the early stages of inflammation the bacteria are attracted. Once activated, neutrophils engulf and destroy bacteria and damaged tissue.

There are two other types of white blood cells, besides neutrophils called macrophages and lymphocytes also engage in the fight against bacteria.

A chemical compound called tumor necrosis factor (TNF) released by the neutrophils activates these cells. Although there are various ways by which neutrophils release TNF, Kettritz and colleagues established that neutrophils could be enthused to produce TNF in a totally new and different way.

“Usually, TNF is produced when specific chemicals bind to proteins called receptors on the surface of a neutrophil, which tells the cell that it should make TNF,” Kettritz says.

“This time, 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.”

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

The team also found that the newly acquired receptors did not work alone. In order to stimulate neutrophils to produce TNF, the GPIIb/IIIa receptor has to work in tandem with the receptor for GM-CSF (the substance produced during the early stages of inflammation).

They also found that the neutrophil produces TNF when GPIIb/IIIa binds to a protein outside the cell called fibronectin and when the GM-CSF receptor binds to GM-CSF.

“We have shown for the first time that platelets can, by using microparticles, help other cells – in this case, neutrophils – respond to inflammation,” Kettritz says. “We also found for the first time that receptors involved in blood clotting also trigger an inflammatory response.”

By targeting the GPIIb/IIIa receptors acquired by neutrophils, new drugs can be devised against several types of inflammation. In particular, the drugs, which are currently being used to prevent blood clotting by inhibiting GPIIb/IIIa receptors on platelets, may now be used against inflammation.

The team tested three of the drugs – abciximab, epifibatide, and tirofiban – on cell cultures in which GPIIb/IIIa receptors was received by neutrophils from platelets. This confirmed the drugs’ effects on inflammation.

The scientists confirmed that all the three drugs inhibited the production of TNF, which reduced inflammation in these cells. The researchers also speculated that some of the beneficial effects of the three drugs on patients with acute coronary syndrome result from their anti-inflammatory properties.

If in clinical trials the drugs’ effects are confirmed, they could be utilised against several types of inflammation that include acute vasculitis, an inflammation of blood vessels that can affect any organ in the body.

The drugs have also been successfully used to treat acute coronary syndrome, which refers to certain types of heart attack and unstable angina.

“The results of this study are very encouraging,” Kettritz says. “Although specific drugs that target GPIIb/IIIa receptor actions on neutrophils may need to be developed in the future, these three drugs can now be tested in clinical trials, which could make them – or modified versions of them – new anti-inflammatory drugs.”

The study is to be published in the September 21 issue of the Journal of Biological Chemistry, was selected as a “Paper of the Week” by the journal’s editors, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance. (With Inputs from ANI)