-
Blood Feb 1996Recently, our laboratory showed that platelets, like leukocytes, roll on activated endothelium expressing P-selectin, thus suggesting a role for P-selectin in hemostasis...
Recently, our laboratory showed that platelets, like leukocytes, roll on activated endothelium expressing P-selectin, thus suggesting a role for P-selectin in hemostasis (Frenette et at, Proc Natl Acad Sci USA 92:7450, 1995). We report here that the P-selectin--deficient mice show a 40% prolongation of the bleeding time on amputation of the tip of the tail. Moreover, defective hemostasis was observed in a local Shwartzman-like reaction induced by skin injections of lipopolysaccharide followed by tumor necrosis factor-alpha in the P-selectin--deficient mice. The hemorrhagic lesions, quantitated both macroscopically and microscopically, were twofold larger in the P-selectin--deficient mice. This was also confirmed by measuring the radioactivity in the skin using chromium-labeled red blood cells. Therefore, it is evident that P-selectin plays a role in hemostasis as suggested by its support of platelet rolling.
Topics: Animals; Bleeding Time; Hemorrhage; Hemostasis; Male; Mice; Mice, Inbred C57BL; P-Selectin; Shwartzman Phenomenon
PubMed: 8608210
DOI: No ID Found -
Infection and Immunity Aug 1999Previously we reported that the consecutive injection of lipopolysaccharide (LPS) into LPS-sensitized mice for the generalized Shwartzman reaction (GSR) appeared to...
Previously we reported that the consecutive injection of lipopolysaccharide (LPS) into LPS-sensitized mice for the generalized Shwartzman reaction (GSR) appeared to induce the injury of renal tubular epithelial cells via apoptosis. The aim of this study was to characterize the mechanism of renal tubular epithelial cell injury in GSR. The expression of Fas and Fas ligand was immunohistochemically detected on renal tubular epithelial cells from GSR-induced mice, although neither Fas nor Fas ligand was found in cells from untreated control mice or in cells from mice receiving a single injection of LPS. GSR-induced renal tubular epithelial cell injury was produced in neither Fas-negative MRL-lpr/lpr mice nor Fas ligand-negative MRL-gld/gld mice. The administration of anti-gamma interferon antibody together with a preparative injection of LPS prevented the expression of Fas and Fas ligand and the apoptosis of renal tubular epithelial cells. A provocative injection of tumor necrosis factor alpha into LPS-sensitized mice augmented Fas and Fas ligand expression and the apoptosis of renal tubular epithelial cells. The administration of tumor necrosis factor alpha to interleukin-12-sensitized mice resulted in Fas and Fas ligand expression and the apoptosis. Sensitization with interleukin-12 together with anti-gamma interferon antibody did not cause the apoptosis of renal tubular epithelial cells. It was suggested that the Fas/Fas ligand system probably plays a critical role in the development of renal tubular epithelial cell injury through apoptotic cell death.
Topics: Animals; Apoptosis; Epithelial Cells; Fas Ligand Protein; Interferon-gamma; Kidney Tubules; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred MRL lpr; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Rabbits; Shwartzman Phenomenon; Tumor Necrosis Factor-alpha; bcl-2-Associated X Protein; fas Receptor
PubMed: 10417181
DOI: 10.1128/IAI.67.8.4112-4118.1999 -
Infection and Immunity Aug 1974Pretreatment with multiple doses of polymyxin B and colistimethate was evaluated as to its ability to sequester sufficient antibiotic in tissues to neutralize the...
Pretreatment with multiple doses of polymyxin B and colistimethate was evaluated as to its ability to sequester sufficient antibiotic in tissues to neutralize the effects of endotoxin in three animal models. Animals were challenged with endotoxin 24, 48, or 72 h after the last dose of antibiotic when there was minimal or not detectable drug in serum. Pretreatment with polymyxin B was successful in preventing the generalized Shwartzman reaction in rabbits and reducing endotoxin lethality in mice; however, large doses (20 mg per kg per day for 2 or 4 days) were required. Prolongation by more than 24 h of the interval between the last dose of polymyxin B and endotoxin challenge resulted in reduction or loss of protection. Dogs were unable to tolerate the high polymyxin B dosage which was protective in the mouse and rabbit. Lower, nontoxic doses of polymyxin B in dogs did not prevent endotoxin shock and lethality, even when challenged as soon as 1 h after the last dose. Pretreatment with colistimethate was ineffective in all three animal models.
Topics: Animals; Colistin; Dogs; Drug Antagonism; Endotoxins; Escherichia coli; Kidney; Kidney Cortex Necrosis; Lethal Dose 50; Lipopolysaccharides; Liver; Mice; Muscles; Polymyxins; Polysaccharides, Bacterial; Premedication; Rabbits; Shock, Septic; Shwartzman Phenomenon
PubMed: 4369040
DOI: 10.1128/iai.10.2.287-292.1974 -
The Journal of Experimental Medicine Apr 1955The cutaneous, ophthalmic, and systemic reactions of normal rabbits to Gram-negative bacterial endotoxins have been compared with the classical reactions of bacterial...
The cutaneous, ophthalmic, and systemic reactions of normal rabbits to Gram-negative bacterial endotoxins have been compared with the classical reactions of bacterial hypersensitivity, and in each case certain similarities have been found. It has also been shown that the Shwartzman phenomenon can be reproduced with tuberculin, in BCG-vaccinated rabbits, and with suspensions or extracts of heat-killed Group A streptococci in rabbits previously sensitized to these bacteria. These considerations suggest the hypothesis that the biologic activity of endotoxins may be based on the existence in "normal" animals of delayed or tuberculin-type hypersensitivity to these materials.
Topics: Animals; Bacteria; Biological Products; Endotoxins; Gram-Negative Bacteria; Hypersensitivity; Hypersensitivity, Delayed; Rabbits; Shwartzman Phenomenon
PubMed: 14354110
DOI: 10.1084/jem.101.4.421 -
The Journal of Experimental Medicine May 1953Cutaneous and systemic infections of rabbits by Group A streptococci bring about a state of preparation for, respectively, the local and generalized Shwartzman...
Studies on the generalized Shwartzman reaction. III. Lesions of the myocardium and coronary arteries accompanying the reaction in rabbits prepared by infection with group A streptococci.
Cutaneous and systemic infections of rabbits by Group A streptococci bring about a state of preparation for, respectively, the local and generalized Shwartzman reactions, produced by intravenous injection of meningococcal or S. marcescens toxin. With maximal systemic streptococcal infections, the lesions of the generalized Shwartzman reaction do not differ from those caused by two successive intravenous injections of Gram-negative bacterial toxins. The characteristic lesions of the reaction are bilateral cortical necrosis of the kidneys, hemorrhagic necrosis in the lungs, liver, and spleen, and myofiber necrosis in the myocardium. Under optimal conditions involving the dosages of streptococci and toxin, and the time interval between the injections, a new lesion consisting of necrosis and the accumulation of fibrinoid material in the walls of the coronary arteries occurred in approximately 50 per cent of animals within 48 hours after the injection of meningococcal toxin. Fibrinoid necrosis was not observed in the arteries of tissues other than the heart. It did not occur in control rabbits injected with streptococci alone or toxin alone, nor in animals with the generalized Shwartzman reaction produced by two intravenous injections of toxin. Streptococcal bacteriemia was present at the time of death in one-third of the animals with fibrinoid necrosis. In one animal, a group of bodies resembling cocci in chains was seen within the wall of a coronary artery with fibrinoid necrosis. A series of photomicrographs to illustrate the pathological changes in the hearts and kidneys of streptococcus-infected rabbits subjected to the Shwartzman reaction is presented.
Topics: Animals; Bacteria; Coronary Vessels; Heart; Hypersensitivity; Myocardium; Necrosis; Rabbits; Sepsis; Shwartzman Phenomenon; Streptococcal Infections; Streptococcus pyogenes
PubMed: 13052831
DOI: 10.1084/jem.97.5.751 -
Infection and Immunity Jul 1985A synthetic compound (506), beta (1-6) D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3'-hydroxyl groups with...
A synthetic compound (506), beta (1-6) D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3'-hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3-hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, exhibited full endotoxic activities identical to or sometimes stronger than those of a reference lipid A from an Escherichia coli Re-mutant (strain F515). Endotoxic activities tested include pyrogenicity and leukopenia-inducing activity in rabbits, body weight-decreasing toxicity in normal mice, lethal toxicity in galactosamine-sensitized mice and chicken embryos, and the preparation and provocation of the local Shwartzman reaction in rabbits. Compound 406, a synthetic counterpart of a biosynthetic precursor of lipid A molecule, showed by contrast only weak activities in all of the above assay systems except for the lethality in galactosamine-loaded mice. This finding strongly suggests that the presence of acyloxyacyl groups at the C-2' and C-3' positions of the disaccharide backbone is one of the most important determinant structures of the lipid A molecule for exhibition of strong biological activities characteristic of lipopolysaccharide and its lipid A moiety. The activities of the corresponding 4'-monophosphate (compound 504) and 1-monophosphate (505) analogs were considerably less than those of the parent molecule 506 and the reference F515 lipid A. Regarding other biological activities, not only compound 506 but also compounds 504, 505, and 406 showed definite activities, sometimes comparable to those of F515 lipid A and other reference natural products. These are the activation of Tachypleus tridentatus amoebocyte clotting enzyme cascade and human complement via the classical pathway, mitogenic and polyclonal B-cell activation of murine splenocytes, stimulation of peritoneal macrophages in a guinea pig, enhancement of migration of human blood polymorphonuclear leukocytes, and induction of a serum factor that is cytostatic and cytocidal to L-929 cells in Mycobacterium bovis BCG-primed mice. Relative potencies of test synthetic compounds depended on the assay systems and varied from one system to another. Dephospho-compound 503 lacked most of the biological activities that were definitely observed with phosphorylated compounds, probably because of its insolubility. This study demonstrates the successful chemical synthesis of an E. coli-type lipid A.
Topics: Adjuvants, Immunologic; Animals; Body Weight; Chemotaxis, Leukocyte; Complement Activation; Endotoxins; Escherichia coli; Fever; Glycoproteins; Leukopenia; Limulus Test; Lipid A; Lymphocyte Activation; Macrophage Activation; Mice; Mice, Inbred Strains; Shwartzman Phenomenon; Structure-Activity Relationship; Tumor Necrosis Factor-alpha
PubMed: 3891627
DOI: 10.1128/iai.49.1.225-237.1985 -
Journal of Bacteriology Feb 1964Fukushi, K. (National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratory, Hamilton, Mont.), R. L. Anacker, W. T. Haskins, M. Landy, K. C. Milner,...
Fukushi, K. (National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratory, Hamilton, Mont.), R. L. Anacker, W. T. Haskins, M. Landy, K. C. Milner, and E. Ribi. Extraction and purification of endotoxin from Enterobacteriaceae: a comparison of selected methods and sources. J. Bacteriol. 87:391-400. 1964.-Endotoxins containing only 0.2% N (accounted for by amino sugars) and 2% ester- and amide-linked fatty acids (calculated as palmitic acid) were prepared from Salmonella enteritidis. These products were of high biological potency, and were rapidly destroyed by acid hydrolysis. Equally potent acid-susceptible products were derived from different strains of Escherichia coli and Serratia marcescens. No correlation was evident between potency and content of nitrogen, fatty acids, and hexosamine; however, low values for carbohydrate were invariably associated with reduced endotoxic activity. Factors such as strain, method of cultivation, and extraction procedure markedly affected the chemical composition and activity of primary extracts. Results are given which demonstrate significant advantages in the use of cell walls for the isolation and purification of endotoxins.
Topics: Carbohydrates; Chemistry Techniques, Analytical; Endotoxins; Enterobacteriaceae; Escherichia coli; Fatty Acids; Hexosamines; Hexoses; Nitrogen; Nucleic Acids; Phosphorus; Pyrogens; Research; Salmonella; Serratia marcescens; Shwartzman Phenomenon
PubMed: 14151062
DOI: 10.1128/jb.87.2.391-400.1964 -
The American Journal of Pathology Aug 1986Renal cortical necrosis (RCN) has been reported in the normal kidney of patients with a contralateral ureteral occlusion (UO). So far, studies have examined the...
Renal cortical necrosis (RCN) has been reported in the normal kidney of patients with a contralateral ureteral occlusion (UO). So far, studies have examined the mechanisms protecting the affected kidney from glomerular thrombosis and cortical necrosis; but to the authors' knowledge, none has ever investigated the potential role of UO on the occurrence of the associated disseminated intravascular coagulation (DIC) episode leading to RCN. Female rats with a ligature of the right or left ureter were given injections, at different times after surgery, of 400 micrograms Salmonella typhosa 0901 endotoxin. Other experimental groups included normal and sham-operation rats and animals with a unilateral nephrectomy or with one kidney rendered ischemic by complete ligature of the renal vessels and of the ureter. All the animals were sacrificed 4 hours after endotoxin, and kidney sections stained with PTAH were examined for the presence of fibrin thrombi. Glomerular thrombosis was never observed in any hydronephrotic kidney, but occurred with a low incidence (16%) in the contralateral organ in the group given endotoxin the second day after UO. The incidence and severity of glomerular capillary thrombosis gradually increased in the normal kidney as the delay between surgery and endotoxin was prolonged; the incidences (P less than 0.01) were 45% and 83%, respectively, after 6 and 10 days. Endotoxin failed totally to initiate the lesion 1 day after UO as well as in normal, sham-operation and unilaterally nephrectomized rats, and in animals with combined UO and ligature of the renal circulation. We conclude that the perfused hydronephrotic kidney liberates a factor(s) that sensitizes to DIC and glomerular thrombosis, typical of the generalized Shwartzman reaction.
Topics: Animals; Capillaries; Endotoxins; Female; Immunization; Kidney; Kidney Glomerulus; Rats; Salmonella typhi; Shwartzman Phenomenon; Thrombosis; Ureteral Obstruction
PubMed: 3740212
DOI: No ID Found -
The American Journal of Pathology Apr 1981Acute and extensive hepatic cell necrosis was produced experimentally in rabbits by means of the Shwartzman mechanism using adeno- and hepatitis B viruses. The change...
Acute and extensive hepatic cell necrosis was produced experimentally in rabbits by means of the Shwartzman mechanism using adeno- and hepatitis B viruses. The change that occurred in the liver was quite severe, namely, areas of hemorrhagic necrosis of various sizes in gross appearance and lytic-coagulative necrosis with hemorrhage and leukocyte-mononuclear cell infiltration histologically. Thrombi formation was noted in and around the necrotic areas, and it was not unusual to see necrosis of an entire lobe. This seems to be a model, to some extent, for human fulminant hepatitis caused by hepatitis virus infection, and suggested that some nonspecific reaction such as intravascular clotting may also play an important role in causing or complicating acute, severe, and extensive necrosis of the liver in human cases. Heparin administration very effectively prevented such hepatic necrosis, which supports the view that the change we observed in the liver was really the Schwartzman reaction; further, it is reminiscent of the fact that heparin administration is sometimes effective in fulminant hepatitis treatment if given at te appropriate stage of the disease.
Topics: Acute Disease; Adenoviruses, Human; Animals; Disease Models, Animal; Female; Hepatitis B; Hepatitis B virus; Hepatitis, Viral, Animal; Liver; Pregnancy; Rabbits; Shwartzman Phenomenon
PubMed: 7223861
DOI: No ID Found -
The American Journal of Pathology Sep 1977A fibrin slide test was utilized to study cutaneous vascular plasminogen activator activity in normal rabbit, rat, monkey, and human skin and in rabbit skin following...
A fibrin slide test was utilized to study cutaneous vascular plasminogen activator activity in normal rabbit, rat, monkey, and human skin and in rabbit skin following development of the local Shwartzman reaction and after substituting epsilon-aminocaproic acid for the preparatory injection of endotoxin in the local Shwartzman reaction. Cutaneous vascular plasminogen activator activity was also studied in rats after attempted induction of the local Shwartzman reaction following inhibition of fibrinolysis with epsilon-aminocaproic acid and/or pregnancy. Plasminogen activator activity was detected in vessels of normal rat, monkey, and human skin but was absent in skin from normal rabbits and rabbits with the local Shwartzman reaction. Intradermal injection of epsilon-aminocaproic acid failed to prepare for the local Shwartzman reaction. In the rat, which has greater cutaneous vascular plasminogen activator activity than the rabbit, inhibition of vascular activator with epsilon-aminocaproic acid and/or pregnancy failed to prepare for the local Shwartzman reaction. These studies indicate that although the markedly diminished level of cutaneous vascular plasminogen activator in the rabbit may be important in the pathogenesis of the local Shwatzman reaction, factors other than inhibition of fibrinolysis are also necessary for preparation of the reaction.
Topics: Aminocaproic Acid; Animals; Blood Vessels; Female; Fibrin; Fibrinolysis; Haplorhini; Humans; In Vitro Techniques; Plasminogen Activators; Pregnancy; Rabbits; Rats; Shwartzman Phenomenon; Skin
PubMed: 407799
DOI: No ID Found