Researchers Find A Potential Key To Human Immune Suppression In Space

The researchers, led by SFVAMC biochemist and former astronautMillie Hughes-Fulford, PhD, identified a signaling pathway called PKAthat in a gravity field responds to the presence of a pathogen bystimulating the expression of 99 genes that in turn cause theactivation of T-cells, which are essential for proper immune function.

Hughes-Fulford found that in the simulated absence of gravity,the PKA pathway did not respond to the pathogen's presence; as aresult, 91 genes were not induced and eight genes were significantlyinhibited, severely reducing the activation of T-cells. The paper waspublished on October 6 in FJ Express, the online rapid-publicationsection of the Journal of the Federation of American Societies forExperimental Biology.

"This is a specific signal pathway that is not working in theabsence of gravity," says Hughes-Fulford, who is also an adjunctprofessor of medicine at the University of California, San Francisco."You're short-circuiting a whole lot of the immune response -- namely,the ability to proliferate T-cells -- which shouldn't be a surprise,because life evolved in Earth's gravity field."

Hughes-Fulford points out that there are only two knownsituations in which T-cell function is so severely compromised: HIVinfection and weightlessness.

The research was conducted on human immune cells in culturethat were placed in a device called a random positioning machine, whichsimulates freefall.

The researchers found that three other pathways which regulateimmune function -- P13K, PKC, and pLAT -- were not affected by theabsence of gravity.

"Why do some pathways work and some not? Perhaps it'sdifferences in the cytoskeleton -- the interior architecture of thecell," speculates Hughes-Fulford. "It's the infrastructure of the cell,a membrane made of lipid, and maybe without gravity it's not aswell-organized as it should be."

Human immune suppression in space was first observed in the1960s and 70s during the Apollo missions conducted by the UnitedStates. As the researchers note in their paper, "15 of 29 Apolloastronauts reported a bacterial or viral infection during [a mission],immediately after, or within 1 week of landing back on Earth."

In 1991, Hughes-Fulford flew on STS-40, the first United Statesspace shuttle mission dedicated to medical research. During thatmission, she participated in experiments that identified T-cells as theparticular components of immune function that were compromised. Hercurrent study is the first to identify a specific mechanism for T-cellsuppression in a weightless environment.

"It's a potential key to understanding the lack of immuneresponse in microgravity, thereby giving us a unique target fortreatment," Hughes-Fulford says. She notes that the problem of immunefunction must be solved if human beings are ever to live and work inspace for extended periods of time.

Hughes-Fulford will continue her research in September, 2006,when Russian cosmonauts carry a custom-designed container housing thesame experiment aboard a Soyuz spacecraft that is scheduled to deliversupplies and experiments to the International Space Station and thenreturn to Earth. "We know how these genes behave in simulatedmicrogravity," she says. "The results from Soyuz should tell us whathappens during spaceflight, in real microgravity."

Other authors of the study include J.B. Boonyaratanakornkit,BS, of UCSF; Augusto Cogoli, PhD, of the Swiss Federal Institute ofTechnology; Chai-Fei Li, BS, of the Northern California Institute forResearch and Education; Thomas Schopper, BS, of the Swiss FederalInstitute of Technology; and Proto Pippia, PhD, and Graci Galleri, PhD,of the University of Sassari, Italy.

The research was supported by NASA grants that were administered byNCIRE, and in part by the U.S. Department of Veterans Affairs.

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