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Researchers find lung-cleansing gene


University scientists have discovered the human version of a gene and gene product that is an essential component of the tiny hair-like whips called cilia that cleanse the lungs. They did it by applying what is known about comparable structures in single-celled organisms that enable the tiny creatures to swim around in pond water.

Such novel work will help other researchers trying to understand and combat chronic lung diseases, the scientists said.

The team used knowledge developed by cell biologists who have studied the cilia of sea urchins and single-celled animals for the past 40 years. To pinpoint the human gene, they combined that knowledge with information generated by international efforts to sequence the human genome -- all genes in the body.

"It turns out that these structures are highly conserved, or repeated, in nature such that the cilia on a one-celled animal in a pond are very, very similar to the respiratory cilia in human airways," said William Reed, research assistant professor of pediatrics at the School of Medicine. "We relied on that high degree of similarity in structure and protein sequence to pull out a human relative of the animal gene."

The gene produces a large protein essential for generating forces that power the whip-like movement of cilia, Reed said. Besides identifying it, they also showed that the gene is "turned on" in cells as they begin growing cilia.

About 80 percent of epithelial cells in healthy human airways are ciliated, he

said. They sweep mucous and trapped particles and disease-causing organisms into the throat where they are usually swallowed

and eliminated.

Ciliated cells can be injured and lost when flu viruses infect the lungs. This reduces the ability of the lungs to cleanse themselves. Normal recovery involves regeneration of the ciliated cells by a repair process that is poorly understood.

The bottom line of the research is that -- now that they have located a human gene "linked" to the appearance of ciliated cells -- they have created a new way of following when ciliated cells appear in the lung, the scientist said.

"In chronic lung diseases such as asthma, the repair process can be slowed or halted," Reed said. "Expression of this gene can be used as a tool to understand the repair process and how it is interrupted in asthmatics."

The gene may also be useful to scientists studying a less common disorder called primary ciliary dyskinesia (PCD), he said. PCD patients' cilia do not move normally. Such people suffer chronic ear and lung infections and can require lung transplants.

A report on the finding appears in the current issue of the American Journal of Respiratory Cell and Molecular Biology. Besides Reed, authors include Johnny L. Carson, Billie M. Moats-Staats, Ping-chuan Hu, Margaret W. Leigh and Albert M. Collier of the departments of pediatrics and cell biology and anatomy, the UNC Center for Environmental Medicine and Lung Biology and the Frank Porter Graham Child Development Center.

Reed called the research, completed last year, "groundwork for quantitatively following airway epithelial cell differentiation." He and his colleagues currently are writing scientific reports on important further developments.

"This is an good example of the way information generated by the Human Genome Project and fundamental cell biology can be combined and translated into a human research setting," he said.

The National Heart, Lung and Blood Institute as well as the U.S. Environmental Protection Agency Office of Research

and Development supported the Carolina experiments.


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