Lung surfactant: Host defense/surface tension, and linking innate/adaptive immune systems

Jo Rae Wright combines the drive and sense of wonderment of an intrepid researcher with a long record of service to the science of physiology. She is Vice Dean for Basic Research, Chief of the Division of Physiology, Department of Cell Biology, and professor of cell biology at Duke University Medical Center.

Recognizing her lifetime achievement as a scientist who practices the "wisdom of the body" concept put forward by Walter B. Cannon, Wright was honored by The American Physiological Society with its Physiology in Perspective Walter B. Cannon Award for her lifetime achievement in physiology. The prize is supported by the Grass Foundation.

Major APS contribution led to Trainee Advisory Committee

Wright's lecture, "Wisdom of lung surfactant: Balancing host defense and surface tension reducing functions," was the keynote event that opened the APS program at its annual Experimental Biology meeting in San Francisco. Cannon was the Society's sixth President, (1914-1916) and was active in APS for nearly 40 years.

In addition to her many past and continuing editorial positions on APS-published journals, Wright was secretary of the Respiration Section (1993-95) and an elected member of APS Council (1999-2002). Wright also led the task force after the 2000 strategic planning meeting that led to formation of the already influential Trainee Advisory Committee.

Asked what she sees as her most important career milestone she focuses on her students and their work: "Ultimately the thing I am most proud of is the accomplishments of my students and fellows," she says. "I really enjoy teaching and the challenge of trying to help them understand what a research experiment is all about without actually doing the research for them. I enjoy helping them make their own discoveries and becoming independent thinkers."

Wright's own career as a "trainee" started in San Francisco after she received her doctorate in physiology (1981) from West Virginia University in her native state. She came to the University of California-San Francisco Medical Center because her advisor at West Virginia told her to go work for "a top" researcher in her area. So Wright came to work for John Clements – and stayed at UCSF for 12 years before leaving for Duke in 1993.

* Physiology in Perspective Lecture Walter B. Cannon Award: "Wisdom of lung surfactant: Balancing host defense and surface tension reducing functions" Saturday, April 1, 5:45 p.m., Convention Center Room 134, Moscone North. Speaker: Jo Rae Wright, Duke University.

Not one to rest on past achievements or laurels, in July 2006 Wright will become Dean of the graduate school of Duke University in North Carolina, and in 2008-09 she will serve as president of the American Thoracic Society.

'70 to 80 years later, new lung surfactant secrets keep popping up'

Wright said she "went into lung surfactant research with Dr. Clements for her post-doctoral work. Surfactants have now been studied for 70 or 80 years and researchers keep learning more and more about their function and mechanism. But new secrets keep popping up."

In what she describes as "a classic example of what physiology is all about," Wright notes that "surfactant study started with a biophysical description that premature babies didn't have proper lung function and opened up a new field of research directed at understanding the role of surfactant components in reducing surface tension."

Then "the dual role of surfactant in host defense evolved from the microscopic observation made by Voss and coworkers that surfactant protein SP-A was structurally homologous with complement component C1q, an immune protein. Thus an understanding of protein structure and function in one system – complement – led to new discoveries in another system -- surfactant," she said.

Surfactant as the link between innate and adaptive immune systems

SP-A and SP-D, which have multiple roles in host defense, are members of a family of innate immune proteins known as collectins, Wright said. They're so-named because the proteins all have a collagen like N-terminal domain and a C-terminal lectin domain. Collectins bind via their lectin domains to sugars and glycolipids on pathogens and opsonize them for uptake by phagocytes. The collectins also regulate the production of inflammatory mediators and reactive species.

"Recent studies from our laboratory as well as other laboratories show that the collectins also play a role in linking innate and adaptive immunity," Wright noted. "Specifically, SP-A has been shown to regulate the maturation of antigen presenting cells, such as dendritic cells, and SP-D regulates the antigen presenting functions of dendritic cells."

Both SP-A and SP-D have been shown to modulate the functions of T-cells. Mice that are deficient in collectins have an enhanced susceptibility to infection and acute lung injury. Additional studies have shown that SP-A and SP-D are degraded by proteases released by immune cells or pathogens leading to inactivation of their host defense functions.

"Taken together, these studies highlight the multiple roles of surfactant in maintaining lung homeostasis and contributing to prevention of lung injury," Wright said, adding that her lab "will largely be defining the link between the two, and their role in airway diseases like asthma.

"The lung is an incredibly challenged organ, Wright added. "Daily we take in 2,750 gallons of air laden with allergens, environmental pollutants and irritants. Yet despite this overwhelming burden most of us don't get lung disease and our lungs almost always effectively carry out gas exchange. Amazing"

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Editor's Note: For further information or to schedule an interview with Jo Rae Wright, please contact Mayer Resnick at the APS newsroom @ 415.905.1024 (March 31-April 5); or 301.332.4402 (cell) or 301.634.7209 (office), mresnick@the-aps.org; or Christine Guilfoy at 978.290.2400 (cell) or 301.634.7253 (office).

A searchable online program for EB is at http://www.faseb.org/meetings/eb2006/call/default.htm

The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has more than 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.

APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In May 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).

Experimental Biology is an annual scientific meeting convened by the Federation of American Societies of Experimental Biology, including the American Physiological Society (APS) and other biomedical societies. The meeting features "nominated" lectures, symposia, research presentations, awards, a job placement center, and an exhibit of scientific equipment, supplies, and publications. This year's participating Societies are APS, American Association of Anatomists, American Society for Biochemistry and Molecular Biology, American Society for Investigative Pathology, American Society for Nutritional Sciences, and the American Society for Pharmacology and Experimental Therapeutics.


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