Magazine article Science News

Plugging Leaks: Manipulating Receptors May Impede Sepsis

Magazine article Science News

Plugging Leaks: Manipulating Receptors May Impede Sepsis

Article excerpt

Using synthetic molecules that bind to signaling proteins on blood vessel cells, scientists have discovered a way to subdue sepsis in mice. They report that activating or disabling the proteins affects the course of sepsis and could provide a way to combat this deadly condition.

Sepsis develops when a blood infection triggers a runaway immune reaction. Patients often become listless or unconscious and show a high fever, rapid heartbeat, and falling blood pressure. Internally, blood leaks through their vessel walls, a catastrophic event that swells nearby tissues. Fluid collects in the lungs, and sluggish blood flow starves organs of nourishment.

Despite decades of research, the biology underlying sepsis has never been fully sorted out, says Athan Kuliopulos, a physician and biochemist at the Tufts University School of Medicine in Boston. Since sepsis has resisted numerous attempts at treatment, some scientists suspect that leakage might stem from some peculiarity of the cells lining blood vessels.

In the 1990s, scientists discovered a protein called protease-activated receptor 1 (PAR1) and three sister proteins on blood vessel cells. As a receptor protein, PAR1 signals its cell when bound by a molecule that fits it.

A receptor typically issues a consistent, predictable signal when activated. "We hypothesized that PAR1 might be changing its role," in sepsis, Kuliopulos says.

He and his colleagues devised synthetic compounds that bind to the receptor, allowing them to switch it on or off. …

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