Severe lung lesions caused by Salmonella are prevented by inhibition of the contact system

Vascular damage induced by trauma, inflammation, or infection results in an alteration of the endothelium from a nonactivated to a procoagulant, vasoc onstrictive, and proinflammatory state, and can lead to lift-threatening co mplications. Here we report that activation of the contact system by Salmon ella leads to massive infiltration of red blood cells and fibrin deposition in the lungs of infected rats. These pulmonary lesions were prevented when the infected animals were treated with H-D-Pro-Phe-Arg-chloromethylketone, an inhibitor of coagulation factor XII and plasma kallikrein, suggesting t hat inhibition of contact system activation could be used therapeutically i n severe infectious disease.