How smoking causes 'destructive' emphysema

How smoking causes 'destructive' emphysema

Exposure to smoking activates genes and portions of the immune system, causing inflammation that triggers life-shortening emphysema, a new study has revealed.

The scientists, including two from The University of Texas MD Anderson Cancer Center, described the track the toxic smoke takes through the tissues and how they accomplish their destructive work.

"It's like walking into a crime scene," said Dr. Farrah Kheradmand, professor of medicine and immunology at BCM and a senior author of the report.

In their current work, the scientists took cells present in the "crime scene" apart, piece by piece to elucidate what occurred when, and how.

It is a complicated story that took more than four years for her, her co-senior author Dr. David Corry and members of their laboratories and colleagues in the Dan L. Duncan Cancer Center at BCM to unravel, she said.

"Previously, emphysema was thought to be a non-specific injurious response to long-term smoke exposure," she said.

"These studies show for the first time that emphysema is caused by a specific immune response induced by smoke.

"It is a combination of little genes affected by an epigenetic factor."

Epigenetics are factors that affect the way genes are expressed after DNA forms. Cigarette smoke is an environmental epigenetic factor.

"If you have enough genes affected by epigenetic factors strung together, it can tip you over into lung damage and emphysema. The inflammation that drives emphysema could also drive cancer development, a testable hypothesis that we have begun to pursue," said Kheradmand.

This study showed that the cigarette recruited antigen-presenting cells (cells that orchestrate the immune system's response to antigens) as co-conspirators in the lung-destroying crime, using specific genes that regulate proteins in their deadly role.
To uncover the cause of tobacco- induced emphysema, they studied mice exposed to conditions that closely simulated how humans smoke.

These animals developed the lung disease in three to four months. Certain inflammatory cells and genes proving crucial to the process, she asserted.

When they analyzed "gene chips" to screen the disease-causing antigen-presenting cells recovered from lungs with emphysema, they uncovered the gene for osteopontin, which promotes initiation of the inflammatory cascade that damages lungs.

Kheradmand added that mice that lacked this gene were resistant to emphysema.

The study has been published in the journal Science Translational Medicine. (ANI)

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