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, vasoconstrictive, and proinflammatory state, and can lead to life-threatening complications. Here we report that activation of the contact system by Salmonella 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 that inhibition of contact system activation could be used therapeutically in severe infectious disease.
Persson
K
K
Department of Cell and Molecular Biology, Lund University, S-221 00 Lund, Sweden.
Mörgelin
M
M
Lindbom
L
L
Alm
P
P
Björck
L
L
Herwald
H
H
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012481:Salmonella Infections, Animal / Q000473:pathology*; D012486:Salmonella typhimurium / Q000472:pathogenicity*
D000590:Amino Acid Chloromethyl Ketones; D000925:Anticoagulants; D001779:Blood Coagulation Factors