How quickly key receptors are activated on blood vessel cells can determine whether one survives or succumbs to sepsis, suggests a report online in Nature Immunology.
Sepsis, a potentially life-threatening immune response to blood-borne infections, leads to loss of blood vessel function, resulting in shock and multiorgan failure. Athan Kuliopulos and colleagues looked to see if inhibition or activation of a receptor called PAR1 could limit the severity of sepsis. Mice injected with bacteria directly into the bloodstream developed sepsis and died; however, these mice were protected if given a PAR1 inhibitor within 4 hours.
The surprise came if PAR1 was inhibited at later times, as this failed to protect these mice; rather, activation of PAR1 at these later times 'protected' mice from toxic shock. The authors show this 'late' activation of PAR1 induces another PAR receptor to become activated. This establishes a protective effect by instructing cells lining the blood vessel to maintain tight junctions and averting the widespread edema and intravascular blood clotting that accompanies shock.
These findings might lead to successful therapies for patients with sepsis and other systemic inflammatory responses.
Athan Kuliopulos (Tufts-New England Medical Center, Boston, MA, USA)
Abstract available online.
(C) Nature Immunology press release.
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