Most exchange of oxygen and carbon dioxide between the body and the environment occurs in the alveoli. Approximately 95% of the alveolar surface is covered by alveolar type I cells, with the remainder made up of type II cells. Type II cells and their role in surfactant secretion have been studied extensively, but much less is known about the role of type I cells, in part due to technical difficulties in obtaining a highly purified type I cell preparation.

The current study uses a powerful DNA microarray technique to obtain the gene expression profile of highly purified type I cells, and then uses the data to infer a novel physiological function for this cell type. In addition to their role in gas exchange, the results suggest that type I cells protect the alveolus from oxidative injury. Moreover, many type I cell-specific genes were identified that could potentially serve as diagnostic markers of acute lung injury, thereby opening up a new field of investigation in alveolar cell biology.

This study began in 2002 in the Lung Biology and Toxicology Laboratory at the Oklahoma State University. When asked about the potential implications of the study, Dr. Lin Liu, director of the lab and one of the authors of the study, said, "With the availability of primary alveolar type I cells and the gene expression profile of this cell type, I believe that more novel functions of type I cells in the lung and new therapeutic targets for pulmonary diseases will be discovered in the near future".

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They then applied their approach to HALP, a gene naturally active in T cells. Dr. Finkel previously discovered and named HALP, an acronym for "HIV-associated life preserver," showing that it had a role in prolonging HIV infection by helping HIV-infected T cells survive attack by the immune system.

Using siRNA and their laboratory techniques, the investigators succeeded in "knocking down," that is, decreasing gene expression by HALP. Because their previous research strongly suggests that HALP promotes latent HIV infection, the new technique has a potential application to HIV treatment. "The siRNA may represent a suicide vector: by knocking down HALP it may allow HIV-infected cells to self-destruct, thus eliminating a hiding place for the virus," said Dr. Finkel.

"More broadly," she added, "the technique could theoretically be directed against other immune-related diseases, by silencing harmful genes active in T cells."

Dr. Finkel's co-authors, all from The Children's Hospital of Philadelphia, were Jiyi Yin, Ph.D., Zhengyu Ma, Nithianandan Selliah, Ph.D., Debra K. Shivers and Randy Q. Cron, M.D., Ph.D. National Institutes of Health grants supported the research, along with support from the University of Pennsylvania Center for AIDS Research and the University's Cancer Center, the Bender Foundation, the Joseph Lee Hollander Chair at The Children's Hospital of Philadelphia, and the W. W. Smith Charitable Trust.

"Effective Gene Suppression Using Small Interfering RNA in Hard-to-Transfect Human T Cells." Journal of Immunological Methods. In press, published online March 24, 2006.

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