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Innate Immunity Nov 2018Ninety years ago, Gregory Shwartzman first reported an unusual discovery following the intradermal injection of sterile culture filtrates from principally Gram-negative... (Review)
Review
Ninety years ago, Gregory Shwartzman first reported an unusual discovery following the intradermal injection of sterile culture filtrates from principally Gram-negative strains from bacteria into normal rabbits. If this priming dose was followed in 24 h by a second intravenous challenge (the provocative dose) from same culture filtrate, dermal necrosis at the first injection site would regularly occur. This peculiar, but highly reproducible, event fascinated the microbiologists, hematologists, and immunologists of the time, who set out to determine the mechanisms that underlie the pathogenesis of this reaction. The speed of this reaction seemed to rule out an adaptive, humoral, immune response as its cause. Histopathologic material from within the necrotic center revealed fibrinoid, thrombo-hemorrhagic necrosis within small arterioles and capillaries in the micro-circulation. These pathologic features bore a striking resemblance to a more generalized coagulopathic phenomenon following two repeated endotoxin injections described 4 yr earlier by Sanarelli. This reaction came to be known as the generalized Shwartzman phenomenon, while the dermal reaction was named the localized or dermal Shwartzman reaction. A third category was later added, called the single organ or mono-visceral form of the Shwartzman phenomenon. The occasional occurrence of typical pathological features of the generalized Shwartzman reaction limited to a single organ is notable in many well-known clinical events (e.g., hyper-acute kidney transplant rejection, fulminant hepatic necrosis, or adrenal apoplexy in Waterhouse-Fredrickson syndrome). We will briefly review the history and the significant insights gained from understanding this phenomenon regarding the circuitry and control mechanisms responsible for disseminated intravascular coagulation, the vasculopathy and the immunopathy of sepsis.
Topics: Allergy and Immunology; Animals; Blood Circulation; Blood Vessels; Disseminated Intravascular Coagulation; Endotoxins; History, 20th Century; History, 21st Century; Humans; Rabbits; Sepsis; Shwartzman Phenomenon
PubMed: 30409091
DOI: 10.1177/1753425918808008 -
Postgraduate Medical Journal Jun 1972
Review
Topics: Acute Disease; Animals; Blood Transfusion; Disseminated Intravascular Coagulation; Heparin; Humans; Liver Diseases; Necrosis; Shwartzman Phenomenon
PubMed: 4558894
DOI: 10.1136/pgmj.48.560.346 -
Canadian Medical Association Journal Jul 1969
Review
Topics: Adrenal Cortex Hormones; Aminocaproates; Anesthesia, Conduction; Blood Transfusion; Chickenpox; Child; Dextrans; Female; Fibrinogen; Ganglia, Autonomic; Heparin; Humans; Hyperbaric Oxygenation; Purpura; Shwartzman Phenomenon
PubMed: 4893497
DOI: No ID Found -
International Journal of Molecular... Jul 2019In recent decades, the elderly population has been rapidly increasing in many countries. Such patients are susceptible to Gram-negative septic shock, namely endotoxin... (Review)
Review
In recent decades, the elderly population has been rapidly increasing in many countries. Such patients are susceptible to Gram-negative septic shock, namely endotoxin shock. Mortality due to endotoxin shock remains high despite recent advances in medical care. The generalized Shwartzman reaction is well recognized as an experimental endotoxin shock. Aged mice are similarly susceptible to the generalized Shwartzman reaction and show an increased mortality accompanied by the enhanced production of tumor necrosis factor (TNF). Consistent with the findings in the murine model, the in vitro Shwartzman reaction-like response is also age-dependently augmented in human peripheral blood mononuclear cells, as assessed by enhanced TNF production. Interestingly, age-dependently increased innate lymphocytes with T cell receptor-that intermediate expression, such as that of CD8CD122T cells in mice and CD57T cells in humans, may collaborate with macrophages and induce the exacerbation of the Shwartzman reaction in elderly individuals. However, endotoxin tolerance in mice, which resembles a mirror phenomenon of the generalized Shwartzman reaction, drastically reduces the TNF production of macrophages while strongly activating their bactericidal activity in infection. Importantly, this effect can be induced in aged mice. The safe induction of endotoxin tolerance may be a potential therapeutic strategy for refractory septic shock in elderly patients.
Topics: Age Factors; Aging; Animals; Humans; Immunity, Innate; Interleukin-12; Lipopolysaccharides; Lymphocytes; Shock, Septic; Shwartzman Phenomenon; Tumor Necrosis Factor-alpha
PubMed: 31269748
DOI: 10.3390/ijms20133260 -
The Surgical Clinics of North America Aug 1968
Review
Topics: Adult; Animals; Cricetinae; Dogs; Female; Histocompatibility; Histocompatibility Testing; Humans; Immunosuppressive Agents; Infant; Infections; Kidney Transplantation; Liver Diseases; Liver Transplantation; Male; Mice; Postoperative Complications; Rats; Shwartzman Phenomenon; Thymectomy; Thymus Gland; Transplantation Immunology; Transplantation, Homologous
PubMed: 4875039
DOI: 10.1016/s0039-6109(16)38585-1 -
Microbiology and Immunology 1985The composition and the nature of the linkage of fatty acids and the Shwartzman activity of lipopolysaccharide (LPS) preparations derived from oral gram-negative... (Comparative Study)
Comparative Study
The composition and the nature of the linkage of fatty acids and the Shwartzman activity of lipopolysaccharide (LPS) preparations derived from oral gram-negative bacteria including Bacteroides gingivalis, Bacteroides loesheii, Eikenella corrodens, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans were examined. 3-Hydroxylated and nonhydroxy fatty acids of various chain lengths were found in all of the LPS preparations. All nonhydroxy fatty acids were found to be ester-bound, and part of the 3-hydroxy fatty acids in the LPS of B. gingivalis, E. corrodens, F. nucleatum, and A. actinomycetemcomitans were shown to be involved in ester linkage. It was also suggested that the hydroxy group of the ester-bound 3-hydroxy fatty acid of the LPS of F. nucleatum and A. actinomycetemcomitans is at least partly substituted by another fatty acid, but in the LPS of B. gingivalis and E. corrodens it is not. The main amide-linked fatty acid of the LPS of B. gingivalis, E. corrodens, F. nucleatum, and A. actinomycetemcomitans was 3-hydroxyheptadecanoic, 3-hydroxydodecanoic, 3-hydroxyhexadecanoic, and 3-hydroxytetradecanoic acid, respectively. The results of the Shwartzman assay showed that the E. corrodens LPS was the most active among the preparations tested, and that the Shwartzman toxicity of Bacteroides LPS is extremely low.
Topics: Actinobacillus; Amino Sugars; Animals; Bacteroidaceae; Bacteroides; Biological Assay; Carbohydrates; Fatty Acids; Fusobacterium; Lipopolysaccharides; Mouth; Rabbits; Shwartzman Phenomenon
PubMed: 4033466
DOI: 10.1111/j.1348-0421.1985.tb00840.x -
The Journal of Experimental Medicine Feb 1965Studies are reported on the effect of immunologically induced thrombocytopenia upon the local and generalized Shwartzman phenomena. Intravenous injection of antiplatelet...
Studies are reported on the effect of immunologically induced thrombocytopenia upon the local and generalized Shwartzman phenomena. Intravenous injection of antiplatelet serum to rabbits produced profound but transient thrombocytopenia unaccompanied by significant changes in circulating leucocytes. Platelet antiserum alone given to rabbits prepared with thorotrast produced renal lesions characteristic of the Shwartzman reaction. Thrombocytopenia induced by platelet antiserum did not inhibit the cutaneous hemorrhagic lesion of the local Shwartzman phenomenon produced by sequential injections of endotoxin intracutaneously and intravenously. The implications of these observations in the pathogenesis of the local cutaneous and generalized Shwartzman reaction are discussed.
Topics: Aminosalicylic Acid; Aminosalicylic Acids; Animals; Blood Platelets; Endotoxins; Immune Sera; Kidney; Leukocyte Count; Leukocytes; Rabbits; Research; Shwartzman Phenomenon; Thorium Dioxide; Thrombocytopenia; Toxicology
PubMed: 14264269
DOI: 10.1084/jem.121.2.235 -
Critical Care Medicine Dec 2013Sepsis, a leading cause of mortality in critically ill patients, is closely linked to the excessive activation of coagulation and inflammation. Protein Z, a cofactor for...
OBJECTIVE
Sepsis, a leading cause of mortality in critically ill patients, is closely linked to the excessive activation of coagulation and inflammation. Protein Z, a cofactor for the protein Z-dependent protease inhibitor, enhances the inhibition of coagulation factor Xa, and protein Z-dependent protease inhibitor inhibits factor XIa in a protein Z-independent fashion. The functions of protein Z and protein Z-dependent protease inhibitor in the inflammatory and coagulant responses to septic illness have not been evaluated.
DESIGN
For induction of generalized Shwartzman reaction, dorsal skinfold chamber-equipped mice were challenged twice with lipopolysaccharide (0.05 mg/kg on day -1 and 5 mg/kg body weight 24 hr later). Time-matched control animals received equal volumes of saline.
SETTING
University research laboratory.
SUBJECTS, INTERVENTIONS, AND MEASUREMENTS
Using intravital fluorescence microscopy in protein Z-dependent protease inhibitor deficient (ZPI) and protein Z deficient (PZ) mice, as well as their wild-type littermates (ZPI, PZ), kinetics of light/dye-induced thrombus formation and microhemodynamics were assessed in randomly chosen venules. Plasma concentrations of chemokine (C-X-C motif) ligand 1, interleukin-6, and interleukin-10 were measured. Liver and lung were harvested for quantitative analysis of leukocytic tissue infiltration and thrombus formation.
MAIN RESULTS
After induction of generalized Shwartzman reaction, all mice showed significant impairment of microhemodynamics, including blood flow velocity, volumetric blood flow, and functional capillary density, as well as leukocytopenia and thrombocytopenia. Thrombus formation time was markedly prolonged after induction of generalized Shwartzman reaction in all mice, except of ZPI mice, which also had a significantly higher fraction of occluded vessels in liver sections. PZ mice developed the highest concentrations of interleukin-6 and interleukin-10 in response to generalized Shwartzman reaction and showed greater leukocytic tissue infiltration than their wild-type littermates.
CONCLUSIONS
In this murine model of generalized Shwartzman reaction, protein Z-dependent protease inhibitor deficiency enhanced the thrombotic response to vascular injury, whereas protein Z deficiency increased inflammatory response.
Topics: Animals; Blood Flow Velocity; Blood Proteins; Chemokine CXCL1; Genotype; Interleukin-1; Interleukin-10; Leukopenia; Lipopolysaccharides; Liver; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Serpins; Shwartzman Phenomenon; Thrombocytopenia; Thrombosis; Venules
PubMed: 23963134
DOI: 10.1097/CCM.0b013e318298a562 -
The Journal of Experimental Medicine Jan 1936The Shwartzman phenomenon can be inhibited by an intravenous injection of a potent bacterial filtrate within a few hours before or after the preparatory intradermal...
The Shwartzman phenomenon can be inhibited by an intravenous injection of a potent bacterial filtrate within a few hours before or after the preparatory intradermal injection. The inhibitory effect is produced non-specifically by filtrates potent in the elicitation of the Shwartzman phenomenon, and it is of a transitory nature. The relation of the observation described to anaphylactic desensitization and to its clinical significance is discussed in this paper.
PubMed: 19870460
DOI: 10.1084/jem.63.1.59 -
Infection and Immunity Feb 1975Endotoxic lipopolysachharide (LPS) was obtained from phenol-water extraction of cell walls prepared from mass-cultivated Fusobacterium necrophorum. The LPS was...
Endotoxic lipopolysachharide (LPS) was obtained from phenol-water extraction of cell walls prepared from mass-cultivated Fusobacterium necrophorum. The LPS was relatively free of nucleic acids and low in protein, and constituted about 4% of the cell walls. Upon acid hydrolysis, some of the components detected were hexosamines (7.0%), neutral and reducing sugars (50.5%), heptose (6.4%), 2-keto-3-deoxyoctonate (0.8%), lipid A (21.0%), and phosphorus (1.7%). Under electron microscopy the LPS appeared mainly as ribbon-like trilaminar structures, and upon chemical treatment it displayed a behavior resembling that reported in certain enterobacterial LPS. The LPS was lethal to mice, 11-day-old chicken embryos, and rabbits. Endotoxicity in mice was enhanced at least 1,380-fold by the addition of 12.5 mug of actinomycin D. Induced tolerance to lethal effect of the endotoxin and rapidly acquired resistance to infection by F. necrophrum viable cells were also demonstrated in mice. The endotoxin produced both localized and generalized Shwartzman reactions as well as biphasic pyrogenic responses in rabbits. These results firmly establish the presence of a classical endotoxin in F. necrophorum, thus providing strong support to our recent suggestion that cell wall-associated components may contribute significantly to the pathogenicity of F. necrophorum.
Topics: Animals; Bacterial Proteins; Cell Wall; Chick Embryo; Dactinomycin; Endotoxins; Female; Fusobacterium; Heptoses; Hexosamines; Immune Tolerance; Immunity; Immunization; Lethal Dose 50; Lipopolysaccharides; Mice; Microscopy, Electron; Phenols; Phosphorus; Polysaccharides, Bacterial; Pyrogens; Rabbits; Shwartzman Phenomenon
PubMed: 1112618
DOI: 10.1128/iai.11.2.371-379.1975