Researchers traced the harmful effects of cigarette smoking from the moment the puff begins to fatal emphysema.

"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. Corry is professor and chief of the section of immunology, allergy and rheumatology in the department of medicine at BCM and a member of the faculty at the Michael E. DeBakey VA Medical Center.
"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," she said. Epigenetics are factors that affect the way genes are expressed after DNA forms. Cigarette smoke is an environmental epigenetic factor.
"DNA is written in pen," said Kheradmand, using a metaphor. "Epigenetics is written in pencil. 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."
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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 said.
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"But when we took them out, the inflammation worsened. The gamma delta T-cells went there to dampen the inflammation," she said. "When they become overwhelmed, the disease ensues."
They confirmed that a subset of antigen-presenting cells (cells that present antigen to activate the immune system) are the key to orchestrating the disease. They had first found these cells in studies of human lung tissue. Then, they duplicated that finding in mice.
Dr. Ming Shan, now a postdoctoral associate in Kheradmand's laboratory, then took the cells out of the lungs of the mice with disease and transferred into mice who had never been exposed to cigarette smoke. After three months, these mice showed inflammatory signs indicating that they were on the way to developing lung damage and emphysema.
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. Mice that lacked this gene were resistant to emphysema, said Kheradmand.
Source-Eurekalert