CNS can send out signals to invite autoimmune attacks

[Guest guest]

CNS can send out signals to invite autoimmune attacks

It may sound like a case of blame the victim, but researchers at

Washington University School of Medicine in St. Louis have shown that

cells in the central nervous system can sometimes send out signals

that invite hostile immune system attacks. In mice the researchers

studied, this invitation resulted in damage to the protective

covering of nerves, causing a disease resembling multiple sclerosis.

" It's been clear for quite a while that our own lymphocytes (white

blood cells) have the ability to enter the central nervous system and

react with the cells there, " says , Ph.D., professor of

molecular biology and pharmacology. " Under normal circumstances, the

brain and the immune system cooperate to keep out those cells that

might harm the brain. But in people with multiple sclerosis, they get

in. "

The researchers found that they could prevent destructive immune

cells from entering nervous system tissue by eliminating a molecular

switch that sends " come here " messages to immune cells. Ordinarily,

flipping that switch would cause immune cells to rush to the vicinity

of the cells that sent the signals and destroy whatever they consider

a danger — including nerve cell coatings.

But in the mice in which the switch was removed, the researchers saw

that immune cells previously primed by the scientists to attack the

central nervous system (CNS) did not enter the CNS, and the mice

stayed healthy.

In contrast, normal mice treated with the same hostile immune cells

had numerous immune cells in their CNS tissue and developed symptoms

similar to multiple sclerosis.

" What allows the primed lymphocytes into the CNS are signals from the

CNS asking them in, " says. " We determined that the

astrocytes, the specialized cells that provide nutrients to neurons,

are among the cells most active in sending signals to attract

lymphocytes. "

The molecular switch that sends the call to immune cells is termed

the tumor necrosis factor receptor (TNFR). When TNFR is activated, it

causes cells to send out signal molecules called chemokines that

direct immune cells to the site of damage or infection. The

researchers found that astrocytes in mice were producing chemokines

in response to activation of their TNFR molecules.

TNFR activation also makes the astrocytes bristle with specific

adhesion molecules that act like Velcro to bind to similar molecules

on the surface of the immune cells. That allows the immune cells that

are attracted by the chemokines to stick around and do more harm.

One of the most promising new drugs for treating multiple sclerosis,

natalizumab (tradename Tysabri), works by blocking the ability of the

immune cells to stick in the CNS through this Velcro mechanism,

notes. Natalizumab is being tested in clinical trials and

appears to be much better at preventing the nerve cell destruction

associated with multiple sclerosis than previous therapies.

" Experiments by others suggested that natalizumab prevented immune

cells from crossing the blood-brain barrier — it was thought to

prevent the cells from leaving the blood stream, " says. " We

are working on that question, and we think that it doesn't

necessarily prevent them from getting out of the blood, but it does

keep them from getting further into the brain. The immune cells pile

up in the space around the blood vessels. This space, the

perivascular space, serves as a gatekeeper to determine what gets in

and what doesn't. "

Next, the research team will study various regions of the brain to

determine the types of signals sent to and from different areas of

the CNS to the immune system.

http://www.rxpgnews.com/research/neurosciences/demyelinatingdiseases/

multiplesclerosis/printer_4477.shtml