Abstract
The hypotension and disseminated intravascular coagulation (DIC) in bacteremia is thought to be mediated by the combined actions of cytokines, prostaglandins, and complement. The contact system, via the release of bradykinin and the activation of Factor XI, has been postulated to be contributing to the observed hypotension and DIC. Using a mAb to Factor XII (C6B7), we blocked the activation of the contact system in an established experimental baboon model in which Escherichia coli was infused to produce lethal bacteremia with hypotension. The untreated group (n = 5) displayed contact activation, manifested by a significant decrease in high molecular weight kininogen (HK) and a significant increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-Kal). The C6B7-treated group (n = 5) showed an inactivation of Factor XII and the changes in HK and alpha 2M-Kal complexes were prevented. Both groups developed DIC manifested by a decrease in platelet, fibrinogen, and Factor V levels. The untreated group developed irreversible hypotension. The treated group experienced an initial hypotension that was reversed and extended the life of the animals. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system, and specific antibody therapy can modulate both the pathophysiological and biochemical changes.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Colman R. W., Edelman R., Scott C. F., Gilman R. H. Plasma kallikrein activation and inhibition during typhoid fever. J Clin Invest. 1978 Feb;61(2):287–296. doi: 10.1172/JCI108938. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Creasey A. A., Stevens P., Kenney J., Allison A. C., Warren K., Catlett R., Hinshaw L., Taylor F. B., Jr Endotoxin and cytokine profile in plasma of baboons challenged with lethal and sublethal Escherichia coli. Circ Shock. 1991 Feb;33(2):84–91. [PubMed] [Google Scholar]
- De La Cadena R. A., Scott C. F., Colman R. W. Evaluation of a microassay for human plasma prekallikrein. J Lab Clin Med. 1987 May;109(5):601–607. [PubMed] [Google Scholar]
- Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
- Harpel P. C., Lewin M. F., Kaplan A. P. Distribution of plasma kallikrein between C-1 inactivator and alpha 2-macroglobulin in plasma utilizing a new assay for alpha 2-macroglobulin-kallikrein complexes. J Biol Chem. 1985 Apr 10;260(7):4257–4263. [PubMed] [Google Scholar]
- Hinshaw L. B., Tekamp-Olson P., Chang A. C., Lee P. A., Taylor F. B., Jr, Murray C. K., Peer G. T., Emerson T. E., Jr, Passey R. B., Kuo G. C. Survival of primates in LD100 septic shock following therapy with antibody to tumor necrosis factor (TNF alpha). Circ Shock. 1990 Mar;30(3):279–292. [PubMed] [Google Scholar]
- Kaufman N., Page J. D., Pixley R. A., Schein R., Schmaier A. H., Colman R. W. Alpha 2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis. Blood. 1991 Jun 15;77(12):2660–2667. [PubMed] [Google Scholar]
- Kerbiriou D. M., Griffin J. H. Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma. J Biol Chem. 1979 Dec 10;254(23):12020–12027. [PubMed] [Google Scholar]
- Mason J. W., Kleeberg U., Dolan P., Colman R. W. Plasma kallikrein and Hageman factor in Gram-negative bacteremia. Ann Intern Med. 1970 Oct;73(4):545–551. doi: 10.7326/0003-4819-73-4-545. [DOI] [PubMed] [Google Scholar]
- Nuijens J. H., Eerenberg-Belmer A. J., Huijbregts C. C., Schreuder W. O., Felt-Bersma R. J., Abbink J. J., Thijs L. G., Hack C. E. Proteolytic inactivation of plasma C1- inhibitor in sepsis. J Clin Invest. 1989 Aug;84(2):443–450. doi: 10.1172/JCI114185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Donnell T. F., Jr, Clowes G. H., Jr, Talamo R. C., Colman R. W. Kinin activation in the blood of patients with sepsis. Surg Gynecol Obstet. 1976 Oct;143(4):539–545. [PubMed] [Google Scholar]
- PROCTOR R. R., RAPAPORT S. I. The partial thromboplastin time with kaolin. A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol. 1961 Sep;36:212–219. doi: 10.1093/ajcp/36.3.212. [DOI] [PubMed] [Google Scholar]
- Pixley R. A., Colman R. W. Purification of human factor XII from plasma using zinc chelate affinity chromatography. Thromb Res. 1986 Jan 1;41(1):89–98. doi: 10.1016/0049-3848(86)90282-3. [DOI] [PubMed] [Google Scholar]
- Pixley R. A., DeLa Cadena R. A., Page J. D., Kaufman N., Wyshock E. G., Colman R. W., Chang A., Taylor F. B., Jr Activation of the contact system in lethal hypotensive bacteremia in a baboon model. Am J Pathol. 1992 Apr;140(4):897–906. [PMC free article] [PubMed] [Google Scholar]
- Pixley R. A., Schapira M., Colman R. W. The regulation of human factor XIIa by plasma proteinase inhibitors. J Biol Chem. 1985 Feb 10;260(3):1723–1729. [PubMed] [Google Scholar]
- QUICK A. J. The assay and properties of labile factor (factor V). J Clin Pathol. 1960 Nov;13:457–462. doi: 10.1136/jcp.13.6.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott C. F., Colman R. W. A simple and accurate microplate assay for the determination of factor XI in plasma. J Lab Clin Med. 1988 Jun;111(6):708–714. [PubMed] [Google Scholar]
- Taylor F. B., Jr, Chang A. C., Peer G. T., Mather T., Blick K., Catlett R., Lockhart M. S., Esmon C. T. DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage. Blood. 1991 Jul 15;78(2):364–368. [PubMed] [Google Scholar]
- Taylor F. B., Jr, Chang A., Esmon C. T., D'Angelo A., Vigano-D'Angelo S., Blick K. E. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest. 1987 Mar;79(3):918–925. doi: 10.1172/JCI112902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor F. B., Jr, Chang A., Ruf W., Morrissey J. H., Hinshaw L., Catlett R., Blick K., Edgington T. S. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock. 1991 Mar;33(3):127–134. [PubMed] [Google Scholar]
- Taylor F. B., Jr, Emerson T. E., Jr, Jordan R., Chang A. K., Blick K. E. Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circ Shock. 1988 Nov;26(3):227–235. [PubMed] [Google Scholar]
- Taylor F., Chang A., Ferrell G., Mather T., Catlett R., Blick K., Esmon C. T. C4b-binding protein exacerbates the host response to Escherichia coli. Blood. 1991 Jul 15;78(2):357–363. [PubMed] [Google Scholar]
- Tuszynski G. P., Knight L., Piperno J. R., Walsh P. N. A rapid method for removal of [125I]iodide following iodination of protein solutions. Anal Biochem. 1980 Jul 15;106(1):118–122. doi: 10.1016/0003-2697(80)90126-8. [DOI] [PubMed] [Google Scholar]
- Ziegler E. J., Fisher C. J., Jr, Sprung C. L., Straube R. C., Sadoff J. C., Foulke G. E., Wortel C. H., Fink M. P., Dellinger R. P., Teng N. N. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med. 1991 Feb 14;324(7):429–436. doi: 10.1056/NEJM199102143240701. [DOI] [PubMed] [Google Scholar]