Blocking protein may prevent smoke-induced lung damage

London, March 19 : A new research has found that blocking a certain protein can reduce or prevent cigarette smoke-induced lung inflammation in mice.

Inflammation results in chronic obstructive pulmonary disease (COPD) and many other smoking-related ailments.

Cigarette smoke triggers the release of Granulocyte macrophage-colony stimulating factor (GM-CSF), which is linked to growth, activation and survival of leukocytes directly implicated in the pathogenesis of COPD.

It also causes activation and recruitment of more inflammatory cells into the lung, thereby perpetuating the inflammatory response and exacerbating ongoing inflammation.

These activated and recruited inflammatory cells also release proteases such as matrix metalloproteinase (MMP)-12, which destroy the lung tissue, resulting in emphysema.

The researchers from the University of Melbourne set out to determine whether blocking GM-CSF could reduce the inflammation and other deleterious effects of cigarette smoke exposure in mice.

They exposed a group of mice, half of which had been treated with a GM-CSF blocking agent, anti-GM-CSF, and half of which were controls, to the equivalent of nine cigarettes of smoke each day for four days. At the end of four days, the mice were killed and their lung tissue was examined for the presence of inflammatory cells.

Lead researcher on the study, Ross Vlahos, a senior research fellow with the lung disease research group at the University of Melbourne, said:

"We found that anti-GM-CSF strongly reduced the number of potentially harmful white blood cells that infiltrate the lung after smoke exposure, as well as inhibiting the pro-inflammatory cytokine tumor necrosis factor (TNF)-?, the chemokine macrophage inflammatory protein-2 (MIP-2), which coordinates the movement of white blood cells into the lung. It also inhibited the protease MMP-12, which is known as one of the main enzymes able to destroy lung tissue.

"Cigarette smoke-exposed mice that were treated with an anti-GM-CSF had significantly less lung inflammation in comparison to untreated mice. This indicates that GM-CSF is a key mediator in smoke-induced lung inflammation and its neutralization may have therapeutic implications in diseases such as COPD."

He added: "Short-term models often translate into benefits in longer-term models. We still need to develop new methods and agents to test this idea long term and we also need to learn if it is effective in reversing longstanding disease.

Now, Dr. Vlahos plans to test whether GM-CSF could be a key target in other disease processes.

He concluded: "We want to understand exactly how blocking GM-CSF alters disease processes at the cellular and molecular levels so we can use this fine detail to make other treatments.

"Our treatment deals with cigarette smoke-induced lung inflammation involved in COPD, not cancer and other smoking-related ailments. Quitting remains the best and only cure for smoking-related lung disease."

The study will soon be published in the American Thoracic Society''s American Journal of Respiratory and Critical Care Medicine.