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oops sorry! Sharon beat me to it!

doris

>

> UC Study With Mice Links Thimerosal With Immune System Dysfunction

>

> From a UC announcement.

>

> Note: Thimerosal is a form of mercury widely used as a

> preservative in pediatric vaccines. Mercury, particularly

> the organic form of mercury such as thimerosal, is known for

> its harmful effect on the nerve systems. Some studies linked

> thimerosal with autism while some others disproved any link.

> Autism or not, thimerosal is toxic and causes damage to

> the nerve system. The only thing uncertain is whether such

> damage would manifest itself clinically.

>

>

> A team of cell biologists, toxicologists and molecular

bioscientists

> at the University of California, , has published a study connecting

> thimerosal with disruptions in antigen-presenting cells known as

dendritic

> cells obtained from mice.

> The study provides the first evidence that dendritic cells show

> unprecedented sensitivity to thimerosal, resulting in fundamental

changes in

> the immune system's ability to respond to external factors.

> The study was published online today and will be available in

the July

> print edition of Environmental Health Perspectives, the peer-reviewed

> scientific publication of the National Institute of Environmental Health

> Sciences.

> " This is the first time that thimerosal has been shown to

selectively

> alter the normal functions of dendritic cells, " said Isaac Pessah, a

> toxicologist with the UC School of Veterinary Medicine,

director of

> the Children's Center for Environmental Health and Disease

Prevention and

> senior author of the study. " Dendritic cells play pivotal roles in

> overcoming viral and bacterial invaders by coordinating the immune

system's

> overall combat response. " One dendritic cell can activate as many as 300

> T-cells white blood cells that help find and kill external agents that

> attack the immune system making them the most effective immune system

> activators.

> The study shows how intricate connections between calcium

channels in

> dendritic cells change when exposed to thimerosal. " The slightest

> fluctuation in how calcium channels `communicate' can alter the growth,

> maturation and activation of dendritic cells, " explained Pessah.

" Thimerosal

> dramatically alters how two key calcium channels, code-named RyR1

and IP3R1,

> found in dendritic cells function as a team by `garbling' the normal

> signaling system between them. "

> When thimerosal at a concentration as low as 20 parts per billion

> alters the fidelity of normal calcium signals, dendritic cells show

abnormal

> secretion of IL-6 cytokine a potent chemical signal that initiates

> inflammatory responses. Higher concentrations 200 parts per billion

> causes programmed death of dendritic cells, preventing them from

maturing

> and doing their primary job of activating T-cells.

> Without proper feedback to guide its response, a normal

dendritic cell

> can quickly become " a rogue, producing misinformation that could

activate

> aberrant and harmful immune responses, " Pessah explained.

> " Even one rogue dendritic cell can activate many inappropriate

immune

> responses. "

> The research team conducted the study on cells cultured from a

strain

> of mouse not particularly susceptible to immune dysregulation. Using

> fluorescent stains and powerful microscopes to study both immature and

> mature dendritic cells from bone marrow cultured under normal

physiological

> conditions, the researchers discovered that extremely small levels of

> thimerosal interfere significantly with calcium channel function

after just

> a few minutes of exposure. They also observed that immature

dendritic cells

> are particularly sensitive to thimerosal.

> Thimerosal is a cheap and effective mercury-based

preservative. Its

> potential effects on embryonic neuron development led to its removal

from

> many pediatric vaccines, however it is still used in influenza,

diphtheria

> and tetanus vaccines, blood products and many over-the-counter

> pharmaceuticals. The concentrations of thimerosal used by the UC

> researchers were comparable to those attained in childhood vaccinations

> containing the preservative.

> Researchers and parents have previously proposed links between

> childhood vaccines and autism, a neurodevelopmental disorder that

affects

> language skills and social interactions. In addition to being a direct

> neurotoxicant, the UC study indicates that thimerosal may also

be an

> immunotoxicant, leaving the immune system vulnerable to microbes and

other

> external influences.

> " Our findings do not directly implicate thimerosal as a single

> causative agent for triggering neurodevelopmental disorders such as

autism, "

> Pessah said. " There is growing evidence that autism is several disorders

> that we now refer to as just one. There is also growing evidence

that some

> children with autism have unique immune cell composition and

responses to

> antigens. The results of our work provide a framework to test the

hypothesis

> that the genetic background of some individuals may render them

especially

> susceptible to thimerosal. "

> Other experts also advise drawing no final conclusions regarding

> thimerosal and autism based on these outcomes.

> " These findings should be interpreted cautiously. Although they

> suggest that thimerosal may affect dendritic cell function, the

> pathophysiological consequences of thimerosal remain unclear, " said

A.

> Schwartz, a physician and director of the National Institute of

> Environmental Health Sciences.

> Since cell functions can differ across organisms, Pessah will next

> study dendritic cells isolated from the blood of children with and

without

> autism to confirm if the intercellular changes are the same in

humans. The

> initial mouse study was funded by the National Institute of

Environmental

> Health Sciences and the UC M.I.N.D. Institute.

> Joining Pessah on the scientific team were molecular bioscientists

> R. Goth, Ruth A. Chu and Gennady Cherednichenko and pathologist

> P. Gregg.

> A copy of " Uncoupling of ATP-mediated Calcium Signaling and

> Dysregulated IL-6 Secretion in Dendritic Cells by Nanomolar

Thimerosal " can

> be downloaded at http://www.ehponline.org/docs/2006/8881/abstract.html.

>

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