"An NFATc3 inhibitor, given as a drug to people in septic shock, may be a way to ease the harmful effects that come with an overproduction of nitric oxide, he added."
New York, June 22 - A team of researchers has discovered how a protein molecule in cells of the immunity system promotes the production of nitric oxide, that helps defend the body from microbial attack.

The protein may offer a target for reining in the inflammatory response, which must be able to fight infection without damaging the tissues.

NFATc3 is one of several related protein molecules known to play a role in regulating genes in the T and B cells of the immune system.

We wanted to know if NFATc3 also had any function in macrophages, which are specialised killer cells that hunt down, engulf and destroy invading bacteria, said Indian-American scientist Ravi Ranjan from University of Illinois at Chicago.

Our study demonstrates that NFATc3 is required for macrophages to effectively fight infection, because without it, they can't make their primary bactericidal agent - nitric oxide, he added.

Macrophages kill using chemicals, including nitric oxide, which they synthesise in response to infection.

Macrophages are also important in reducing the inflammation in sepsis, an out-of-control reaction to infection that can cause organ failure and death.

When the researchers exposed macrophages to chemicals that signal a bacterial infection, they found that NFATc3 increasingly bound to genes that boost the production of nitric oxide synthase - the enzyme that makes nitric oxide.

The binding of NFATc3 suggests the molecule is turning on those genes and upping the production of nitric oxide.

Macrophages deficient in NFATc3 produced much less nitric oxide synthase under the same conditions.

Without the ability to synthesise inducible nitric oxide synthase, a macrophage would be missing a key element of its chemical weaponry, Ranjan explained.

We would expect these cells to be much less effective at killing bacteria and easing sepsis, he added.

The immune system must strike a balance between fighting infection and going overboard as it does in sepsis and actually causing harm, Ranjan said.

An overproduction of nitric oxide can actually contribute to lung injury even as it helps clear bacterial infections.

An NFATc3 inhibitor, given as a drug to people in septic shock, may be a way to ease the harmful effects that come with an overproduction of nitric oxide, he added.

The study was published in Journal of Innate Immunity.


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