1.Single-chain factor XII exhibits activity when complexed to polyphosphate.
Engel R1, Brain CM, Paget J, Lionikiene AS, Mutch NJ. J Thromb Haemost. 2014 Sep;12(9):1513-22. doi: 10.1111/jth.12663. Epub 2014 Aug 13.
BACKGROUND: The mechanism underpinning factor XII autoactivation was originally characterized with non-physiological surfaces, such as dextran sulfate (DS), ellagic acid, and kaolin. Several 'natural' anionic activating surfaces, such as platelet polyphosphate (polyP), have now been identified.
2.The T cell-specific serine proteinase TSP-1 is associated with cytoplasmic granules of cytolytic T lymphocytes.
Fruth U, Prester M, Golecki JR, Hengartner H, Simon HG, Kramer MD, Simon MM. Eur J Immunol. 1987 May;17(5):613-21.
This study describes the localization of the previously purified T cell-specific serine proteinase, termed TSP-1 (M. M. Simon et al., EMBO J. 1986. 5: 3267), within cytoplasmic granules of cytolytic T cell lines (CTLL). Subcellular fractionation of disintegrated CTLL (ruptured by nitrogen cavitation) was accomplished by Percoll density gradient centrifugation of cell lysates (postnuclear supernatant). Individual fractions were tested for proteinase activity on chromogenic peptide substrates and for the presence of TSP-1 by Western blot analysis. In addition, each fraction was assayed for cytolytic activity against sheep red blood cells (SRBC), for protein and for additional marker enzymes to assess the enrichment for cellular organells. All serine enzyme-type molecules including TSP-1 expressed by CTLL were identified by labeling cell lysates or gradient fractions with the serine proteinase-specific affinity ligand tritiated diisopropyl fluorophosphate [( 3H]DFP) in the presence or in the absence of class-specific or enzyme-specific proteinase inhibitors and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
3.Severe lung lesions caused by Salmonella are prevented by inhibition of the contact system.
Persson K1, Mörgelin M, Lindbom L, Alm P, Björck L, Herwald H. J Exp Med. 2000 Nov 20;192(10):1415-24.
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.
