Platelet Factor 3 and the Generalized Shwartzman Reaction^[*]

Summary

The mechanism of “provocation” of the generalized Shwartzman reaction was studied in rats and rabbits. Rats were “prepared” for the reaction by epsilon-aminocaproic acid or pregnancy, rabbits by Thorotrast or endotoxin. Infusions of different preparations of platelet factor 3 activity were not capable of “provoking” the Shwartzman reaction. Purified bovine platelet factor 3, rabbit brain tissue extracts in the form of “so-called” partial thromboplastin or a soya bean phospholipid preparation were used. The results suggest that in addition to the aggregation of platelets and the release of platelet factor 3 other actions of endotoxin are essential to the production of the generalized Shwartzman reaction.

^* Aided by Grants HE-05666-06 and 5 T1 GM-865-05 from the National Institutes of Health, United States Public Health Service.

• References

• 1 McKay D. G, Gitlin D, Craig J. M. Immunochemical demonstration of fibrin in the generalized Shwartzman reaction. Arch. Path. 67: 270 1959;
• 2 Bohle A, Sitte H, Miller F. Elektronenmikroskopische Untersuchungen am Glomerulum des Kaninchens beim generalisierten Shwartzman-Phänomen. Verh. dtsch. Ges. Path. 326 Fischer; Stuttgart: 1958
• 3 McKay D. G, Shapiro S. S. Alterations in the blood coagulation system induced by bacterial endotoxin. I. In vivo (generalized Shwartzman reaction). J. exp. Med. 107: 353 1958;
• 4 Kleinmaier H, Goergen K, Lasch H. G, Krecke H-J, Bohle A. Untersuchungen zur Frage der Gerinnungsstörung beim Sanarelli-Shwartzman-Phänomen (sog. generalisierten Shwartzman-Phänomen) des Kaninchens. Z. ges. exp. Med. 132: 275 1959;
• 5 McKay D. G. Blood coagulation and the generalized Shwartzman reaction. In: Diffuse Intravascular Clotting. Thrombos. Diathes. haemorrh. (Stuttg.), Suppl. 20: 107 1966;
• 6 Lee L. Reticuloendothelial clearance of circulating fibrin in the pathogenesis of the generalized Shwartzman reaction. J. exp. Med. 115: 1065 1962;
• 7 Lee L. Personal communication..
• 8 Linder M. Cited by Lasch, H. G., L. Róka, and D. Heene Experimental intravascnlar clotting. In: Pathogenesis and treatment of thromboembolic diseases. Thrombos. Diathes. haemorrh. (Stuttg.), Suppl. 21: 533 1966;
• 9 Good R. A, Thomas L. Studies on the generalized Shwartzman reaction. IV. Prevention of the local and generalized reactions with heparin. J. exp. Med.. 97: 871 1953;
• 10 Benacerraf B, Sebestyen M. M. Effect of bacterial endotoxins on the reticuloendothelial system. Fed. Proc. 16: 860 1957;
• 11 Beeson P. B. Effect of reticulo-endothelial blockade on immunity to the Shwartzman phenomenon. Proc. Soc. exp. Biol. (N. Y.). 64: 146 1947;
• 12 Beller F. K, Mitchell P. Production of the generalized Shwartzman reaction by protease inhibitors. Fed. Proc. 24: 155 1965;
• 13 Levin J, Beck E. A re-appraisal of the role of blood coagulation and platelets in the generalized Shwartzman phenomenon. Thrombos. Diathes. haemorrh. (Stuttg.). 15: 519 1966;
• 14 Apitz K. A study of the generalized Shwartzman phenomenon. J. Immunol. 29: 255 1935;
• 15 Wong T-C. A study on the generalized Shwartzman reaction in pregnant rats induced by bacterial endotoxin. Amer. J. Obstet. Gynec. 84: 786 1962;
• 16 Unpublished data.
• 17 Margaretten W, Zuriker H. O, McKay D. G. Production of the generalized Shwartzman reaction in pregnant rats by intravenous infusion of thrombin. Lab. Invest 13: 552 1964;
• 18 Kaley G, Demopoulos H, Zweifach B. W. Occlusive vascular lesions induced by bacterial endotoxin in kidneys of pregnant rats. Proc. Soc. exp. Biol. (N. Y.). 109: 456 1962;
• 19 McKay D. G. Disseminated Intravascular Coagulation. An Intermediary Mechanism of Disease. P. B. Hoeber; New York: 1964
• 20 Horowitz H. I, Prez Des R. M, Hook E. W. Effects of bacterial endotoxin on rabbit platelets. II. Enhancement of platelet factor 3 activity in vitro and in vivo. J. exp. Med. 116: 619 1962;
• 21 Lasch H. G, Rodriguez-Erdmann F, Krecke H-J. Quantitative und qualitative Veränderungen der Thrombozyten beim Sanarelli-Shwartzman-Phänomen. Verh. dtsch. Ges. inn. Med. 66: 992 1961;
• 22 Rodriguez-Erdmann F. Studies on the pathogenesis of the generalized Shwartzman reaction. III. Trigger mechanism for the activation of the prothrombin molecule. Thrombos. Diathes. haemorrh. (Stuttg.). 12: 471 1964;
• 23 Schneider C. L. Thromboplastin complications of late pregnancy. In: Toxemias of pregnancy, human and veterinary. 163 A Ciba Foundation Symposium, Blakiston; Philadelphia: 1950
• 24 Müller-Berghaus G, Lasch H. G. Untersuchungen über Beziehungen zwischen Gefäß- und Gerinnungsfaktoren beim Sanarelli-Shwartzman-Phänomen. Thrombos. Diathes. haemorrh. (Stuttg.). 09: 335 1963;
• 25 Horn R. G, Spicer S. S. Sulfated mucopolysaccharide in fibrinoid glomerular occlusions of the generalized Shwartzman reaction. Amer. J. Path. 46: 197 1965;
• 26 McKay D. G. Leukocytes and the generalized Shwartzman reaction (GSR). Fed. Proc. 25: 497 1966;
• 27 Alkjaersig N, Abe T, Seegers W. H. Purification and quantitative determination of platelet factor 3. Amer. J. Physiol. 181: 304 1955;
• 28 Rodriguez-Erdmann F. Über eine einfache Methode zur wiederholten Blutgewinnung beim Kaninchen. Pflügers Arch. 269: 306 1959;
• 29 Biggs R, Douglas A. S, MacFarlane R. G. The formation of thromboplastin in human blood. J. Physiol. 119: 89 1953;
• 30 McKay D. G, Shapiro S. S, Shanberge J. N. Alterations in the blood coagulation system induced by bacterial endotoxins. II. In vitro. J. exp. Med. 107: 369 1958;
• 31 Des Prez R. M, Horowitz H. I, Hook E. W. Effects of bacterial endotoxin on rabbit platelets. I. Platelet aggregation and release of platelet factors in vitro. J. exp. Med. 114: 857 1961;
• 32 Rodriguez-Erdmann F. Intravascular activation of the clotting system with phospholipids. Production of the generalized Shwartzman reaction with platelet factor 3. Blood 26: 541 1965;
• 33 Epstein E, Quick A. J. Effect of injecting platelet extract intravenously. Proc. Soc. exp. Biol. (N. Y.). 83: 453 1953;
• 34 McKay D. G, Rowe F. J. The effect on the arterial vascular system of bacterial endotoxin in the generalized Shwartzman reaction. Lab. Invest 09: 117 1960;
• 35 Palmerio C, Ming S. G, Frank E, Fine J. The role of the sympathetic nervous system in the generalized Shwartzman reaction. J. exp. Med. 115: 609 1962;
• 36 Müller-Berghaus G, McKay D. G. Prevention of the generalized Shwartzman reaction in pregnant rats by alpha-adrenergic blocking agents. In preparation..
• 37 Sanarelli G. De la pathogénie du choléra (Neuvième mémoire). Le choléra expérimental. Ann. Inst. Pasteur. 38: 11 1924;
• 38 Thomas L, Good R. A. Studies on the generalized Shwartzman reaction. I. General observations concerning the phenomenon. J. exp. Med. 96: 605 1952;