Gene that limits damage to lung during trauma or transplant identified

WASHINGTON - Scientists at Washington University School of Medicine in St. Louis have identified a gene that limits damage to the lung during acute stress from illness, trauma or transplant.

They said defects in the bcl3 gene likely leave some patients more vulnerable to lung injury.

The researchers have demonstrated that this critical gene, which is active in bone marrow cells, can prevent lung injury in mice.

The real culprits underlying acute lung injury are infection-fighting white blood cells called neutrophils. When the body makes too many neutrophils, however, they begin to attack healthy tissue, causing even more damage and sometimes, even death.

“In mice, we found that the bcl3 gene essentially controls how many neutrophils the body produces under acute stress in the lung,” said senior author Andrew Gelman.

In a series of experiments in mice undergoing lung transplants, the researchers found that in response to acute stress in the lung, a cytokine called granulocyte colony stimulating factor (G-CSF) accumulates in the blood, which in turn stimulates the production of neutrophils in the bone marrow.

However, there’s a counterbalance built into the system. When G-CSF builds up in the blood, the bcl3 gene is activated in the bone marrow to begin shutting down neutrophil production.

When the scientists transplanted healthy mouse lungs into mice that lacked bcl3 in their bone marrow, things went haywire. Without the gene, neutrophil production went unchecked, and the mice developed acute lung injury.

The bcl3 gene, they showed, acts like a master switch to control the effects of G-CSF on neutrophil production.

The researchers also showed they could prevent acute lung injury in a mouse model of sepsis by blocking G-CSF in mice that lacked bcl3.

The research has been published in the Journal of Clinical Investigation. (ANI)