Science News article - Decoding Sepsis Protein

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Decoding a protein to fend off sepsis

Seppa

From Orlando, Fla., at a meeting of the American Society of Hematology

Sepsis is a lethal blood disorder that typically arises from bacterial

infections. It's marked by organ damage caused by inflammation and blood vessel

leakage. A synthetic version of activated protein C (ACP) is the sole drug

approved to specifically attack sepsis, but it only slightly reduces the risk of

death. Scientists had suggested that APC works by protecting healthy cells from

dying and had found it to have anticoagulant effects.

A study in mice now finds that the anticoagulant property isn't APC's key

attribute—in fact, it might even be a shortcoming. Instead, APC's value stems

from its ability to attach to two proteins on the surface of cells. By binding

to these two receptors, APC inhibits a death signal in a cell, says biologist

Harmut Weiler of the BloodCenter of Wisconsin in Milwaukee.

Weiler notes that the two affected receptors are commonly found on cells that

make up blood vessels. He and his colleagues report that in mice with sepsis

treated with APC, animals that lacked the two receptors were more likely to die

than were mice that had the receptors.

" This is a trailblazing study, " says Khanti R. Rai, a physician at the Long

Island Jewish Medical Center in New Hyde Park, N.Y. It argues for maintaining

the integrity of vessel walls in fighting sepsis, he says.

Weiler's group also discovered a danger of APC's anticoagulant effect. Mice

infected with Staphylococcus aureus all died from sepsis, despite treatment with

standard APC. But when given APC that had been altered to lack the anticoagulant

stimulus, nearly all the mice survived.

The findings could eventually lead to a modified, more potent version of APC,

Weiler says. An APC molecule without anticoagulant properties might enable

doctors to prescribe larger doses, he says.