scholarly journals SIMILARITY OF HOST RESPONSES ELICITED BY POLYSACCHARIDES OF ANIMAL AND PLANT ORIGIN AND BY BACTERIAL ENDOTOXINS

1957 ◽  
Vol 106 (1) ◽  
pp. 77-97 ◽  
Author(s):  
Maurice Landy ◽  
Murray J. Shear ◽  
Keyword(s):  
Host Responses ◽  
Mouse Tissue ◽  
Rabbit Skin ◽  
Biological Phenomena ◽  
Hemorrhagic Necrosis ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Sarcoma 37 ◽  
Kidney Liver ◽  
Plant Sources

Ten polysaccharides, isolated from various animal and plant sources, were selected for comparison with 2 bacterial polysaccharides, typical of Gram-negative endotoxins. The tissue sources were: mouse (kidney, liver, lung, stomach, Sarcoma 37, and Carcinoma 241-6); rabbit skin and chick embryo skin; and tangerine and Bryonia root. The bacterial endotoxins were those of S. typhosa and Serr. marcescens. Their relative potency was determined in inducing the following host effects: fever, tolerance to pyrogenic action, leucocytic changes, the Shwartzman reaction, damage to Sarcoma 37, dermal hemorrhagic-necrosis by epinephrine, enhancement of antibody production, and lethality. Some of the polysaccharides were consistently active in all the host reactions studied; except for pyrogenic activity at high dosage, the other polysaccharides were consistently negative throughout. The mouse tissue polysaccharides elicited all the effects studied; in some instances their potency approached those of the bacterial polysaccharides. It is pointed out that elicitation of the above array of biological phenomena, hitherto considered characteristic of bacterial endotoxins, can be obtained with polysaccharides from animal and plant tissues.

scholarly journals THE PREVENTION OF THE GENERALIZED SHWARTZMAN REACTION WITH SODIUM WARFARIN

1958 ◽  
Vol 107 (3) ◽  
pp. 377-381 ◽  
Author(s):  
Sandor S. Shapiro ◽  
Donald G. McKay
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Control Group ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Intravascular Coagulation ◽  
Intravenous Injections ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Kidney Liver ◽  
Intravenous Sodium

Using intravenous sodium warfarin, rabbits were rendered hypoprothrombinemic and subjected to two intravenous injections of Shear's polysaccharide. None of the 9 animals surviving the required period of time developed bilateral renal cortical necrosis or histologic thrombi in the kidney, liver, spleen, or lungs. In a control group of 7 animals treated only with endotoxin, 6 developed bilateral renal cortical necrosis. It is concluded that the prothrombin complex is necessary for the production of the generalized Shwartzman reaction by bacterial endotoxins and that this phenomenon is essentially a process of disseminated intravascular coagulation.

scholarly journals Biofilm Growth Increases Phosphorylcholine Content and Decreases Potency of Nontypeable Haemophilus influenzae Endotoxins

2006 ◽  
Vol 74 (3) ◽  
pp. 1828-1836 ◽  
Author(s):  
Shayla West-Barnette ◽  
Andrea Rockel ◽  
W. Edward Swords
Keyword(s):  
Haemophilus Influenzae ◽  
Inflammatory Responses ◽  
Opportunistic Pathogen ◽  
Host Responses ◽  
Toll Like Receptor ◽  
Nontypeable Haemophilus Influenzae ◽  
Toll Like Receptor 4 ◽  
Biofilm Growth ◽  
Bacterial Endotoxins ◽  
Cell Layers

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) is a common respiratory commensal and opportunistic pathogen. NTHI is normally contained within the airways by host innate defenses that include recognition of bacterial endotoxins by Toll-like receptor 4 (TLR4). NTHI produces lipooligosaccharide (LOS) endotoxins which lack polymeric O side chains and which may contain host glycolipids. We recently showed that NTHI biofilms contain variants with sialylated LOS glycoforms that are essential to biofilm formation. In this study, we show that NTHI forms biofilms on epithelial cell layers. Confocal analysis revealed that sialylated variants were distributed throughout the biofilm, while variants expressing phosphorylcholine (PCho) were found within the biofilm. Consistent with this observation, PCho content of LOS purified from NTHI biofilms was increased compared to LOS from planktonic cultures. Hypothesizing that the observed changes in endotoxin composition could affect bioactivity, we compared inflammatory responses to NTHI LOS purified from biofilm and planktonic cultures. Our results show that endotoxins from biofilms induced weaker host innate responses. While we observed a minimal effect of sialylation on LOS bioactivity, there was a significant decrease in bioactivity associated with PCho substitutions. We thus conclude that biofilm growth increases the proportion of PCho+ variants in an NTHI population, resulting in a net decrease in LOS bioactivity. Thus, in addition to their well-documented resistance phenotypes, our data show that biofilm communities of NTHI bacteria contain variants that evoke less potent host responses.

scholarly journals SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

2021 ◽  
Author(s):  
Magen E. Francis ◽  
Una Goncin ◽  
Andrea Kroeker ◽  
Cynthia Swan ◽  
Robyn Ralph ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Clinical Symptoms ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Hamster Model ◽  
Organ Systems ◽  
Major Organ ◽  
Kidney Liver ◽  
Multiorgan Disease

AbstractCOVID-19 (coronavirus disease 2019) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

scholarly journals ALTERATIONS IN THE BLOOD COAGULATION SYSTEM INDUCED BY BACTERIAL ENDOTOXIN

1958 ◽  
Vol 107 (3) ◽  
pp. 353-367 ◽  
Author(s):  
Donald G. McKay ◽  
Sandor S. Shapiro
Keyword(s):  
Blood Coagulation ◽  
Marked Decrease ◽  
Fibrinogen Level ◽  
Normal Values ◽  
Bacterial Endotoxin ◽  
Coagulation System ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
The One

The intravenous injection of bacterial endotoxins alter the coagulation system of rabbits' blood in vivo. Twenty-four hours after the first injection the fibrinogen level rises to twice normal values. The second injection at this time causes a 30 to 40 per cent decrease in fibrinogen content in 4 hours. Twenty hours later it again rises to twice normal values. A marked decrease in whole blood coagulation times in silicone occurs 4 hours after both injections but rises to normal values 24 hours following each injection. The circulating platelets drop from average levels of 300,000/c.mm. to 150,000/c.mm. after the first injection. The platelets remain at this low level and decrease to less than 100,000 after the second injection. During this time no fibrinolytic or fibrinogenolytic activity can be detected. Also, there is no significant change in the one stage prothrombin times or antithrombin titres. The marked decrease in circulating fibrinogen at the time when intracapillary thrombi are formed suggests that the "hyaline" thrombi of the generalized Shwartzman reaction are composed, in part, of fibrin. There appears to be a relationship between the level of circulating fibrinogen at the time of injection of bacterial endotoxin and the extent of the thrombosis. The higher the preinjection fibrinogen level, the more extensive is the thrombosis. There is also a relationship between the amount of fibrinogen loss and the extent of thrombosis after the injection. The more extensive the thrombosis the greater is the postinjection decrease in circulating fibrinogen. A comparison between the response of the hemostatic mechanism to tissue thromboplastin and bacterial endotoxin indicates that the latter acts in a unique manner and not by way of a simple "thromboplastic" activity. From the hematological standpoint, "preparation" for the generalized Shwartzman reaction is accompanied by an increased circulating fibrinogen, leukocytosis, and thrombocytopenia.

scholarly journals STRAIN DIFFERENCES IN LOCAL HEMORRHAGIC RESPONSE (SHWARTZMAN-LIKE REACTION) OF MICE TO A SINGLE INTRADERMAL INJECTION OF BACTERIAL POLYSACCHARIDES

1957 ◽  
Vol 105 (6) ◽  
pp. 653-664 ◽  
Author(s):  
Margaret G. Kelly ◽  
Norman H. Smith ◽  
Isidore Wodinsky ◽  
David P. Rall
Keyword(s):  
Strain Differences ◽  
Inbred Strains ◽  
Blocking Agent ◽  
Intradermal Injection ◽  
F1 Hybrid ◽  
Hemorrhagic Necrosis ◽  
Inbred Strains Of Mice ◽  
Anticoagulant Drug ◽  
Shwartzman Reaction ◽  
Hemorrhagic Lesion

A survey of inbred strains of mice was made to determine whether the phenomenon of dermal hemorrhagic necrosis, as described in rabbits by Shwartzman, could be elicited in mice by bacterial polysaccharide preparations of demonstrated activity in rabbits. The polysaccharide preparations used were obtained from cultures of S. marcescens, S. typhosa, Ps. aeruginosa, and H. pertussis. Ten of the strains tested were unreactive. Three strains of mice and one F1 hybrid subline developed a hemorrhagic lesion at the site of injection of a single, relatively high intradermal dose of polysaccharide. Some increase in incidence of hemorrhagic lesions was obtained when the intradermal dose was followed in 24 hours by an intravenous injection. In the gross and microscopically, the skin lesion produced in mice resembled the Shwartzman reaction in rabbits. An adrenergic blocking agent, SY-28, and an anticoagulant drug, coumadin, both of which block the dermal Shwartzman reaction in rabbits, also blocked the hemorrhagic skin reaction in mice.

scholarly journals MODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS

1965 ◽  
Vol 121 (5) ◽  
pp. 751-759 ◽  
Author(s):  
Yoon Berm Kim ◽  
Dennis W. Watson
Keyword(s):  
Standard Dose ◽  
Endotoxin Tolerance ◽  
Immunologic Tolerance ◽  
Host Responses ◽  
Immune Mechanism ◽  
Immunoelectrophoretic Analysis ◽  
Specific Antibodies ◽  
Bacterial Endotoxins ◽  
Exclusion Chromatography

Serum from rabbits rendered tolerant or immune to 100 MPD-3/kg of endotoxin when passively transferred to normal rabbits gave partial tolerance to the standard dose of endotoxin. The same serum was fractionated by DEAE chromatography into 4 major fractions. Immunoelectrophoretic analysis indicated that the 7S γ2-and the 19S γ1-immunoglobulins were separated into two distinct fractions. Of the four fractions tested, only fraction IV containing 19S γ1-immunoglobulm conferred complete pyrogenic tolerance to 100 MPD-3/kg of endotoxin. Additional fractionation of DEAE fraction IV by exclusion chromatography on sephadex G-200 gave 3 fractions. Of these only the first, containing 19S γ1-immunoglobulin conferred complete pyrogenic and lethal tolerance to normal rabbits. There was no correlation between the quantity of O-specific antibodies and the ability to transfer tolerance. It is concluded that endotoxin tolerance involves a classical immune mechanism which includes both 19S γ1-immunoglobulin specific for toxophore groups common to many endotoxins and a normally functioning RES. To avoid confusion with immunologic tolerance, it is suggested that the term endotoxin immunity be substituted for endotoxin tolerance.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1953 ◽  
Vol 97 (6) ◽  
pp. 871-888 ◽  
Author(s):  
Robert A. Good ◽  
Lewis Thomas
Keyword(s):  
Intravenous Injection ◽  
Essential Role ◽  
Vascular Occlusion ◽  
Lethal Effect ◽  
Intradermal Injection ◽  
Cortical Necrosis ◽  
Hemorrhagic Necrosis ◽  
Shwartzman Reaction ◽  
Previously Treated ◽  
Glomerular Capillaries

In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized Shwartzman reactions, the effect of heparin was studied. Aqueous heparin, administered intravenously, and "depot" heparin, injected subcutaneously, prevented completely the occurrence of the local and generalized Shwartzman phenomena. The amounts of heparin required for protection were similar to the amounts required to produce sustained incoagulability of the blood of rabbits for a period of at least 4 hours. The local and generalized Shwartzman reactions were prevented when heparin was given at the time of provocation, but not when heparin was administered during the period of preparation. Heparin prevented the development of bilateral cortical necrosis of the kidneys following a single intravenous injection of meningococcal toxin in rabbits previously treated with cortisone or thorotrast. Hemorrhagic necrosis of the skin which follows an intradermal injection of toxin in thorotrast-treated rabbits was also prevented by heparin. Provocation of the dermal Shwartzman reaction with glycogen, saline suspension of rabbit liver, and human serum was prevented by treatment with heparin. Heparin itself, in the preparations and dosages used, had no consistent effect on either white blood cell or platelet counts. Heparin had no effect on the occurrence of polymorphonuclear leukopenia which follows an intravenous injection of meningococcal toxin. Treatment with heparin did not interfere with the lethal effect of single, large doses of meningococcus toxin. In animals in which bilateral cortical necrosis of the kidneys was prevented by heparin, occlusion of the glomerular capillaries by "fibrinoid" material did not occur. These observations support the concept that vascular occlusion plays an essential role in the development of the local and generalized Shwartzman reactions.

Predisposition to Thrombosis in Experimental Cancer

1975 ◽  
Author(s):  
P. Hilgard
Keyword(s):  
Reticuloendothelial System ◽  
Clinical Findings ◽  
Low Grade ◽  
Malignant Diseases ◽  
Clotting Factors ◽  
Rapid Decomposition ◽  
Experimental Cancer ◽  
Bacterial Endotoxins ◽  
Normal Rat ◽  
Shwartzman Reaction

In accordance with clinical findings in malignant diseases, the growth of allogeneic and autochthonous rat tumours induced characteristic changes of the clotting mechanism of the host: increased activity of various clotting factors and elevation of plasma fibrinogen levels, yet the presence of high amounts of serum FDP and an accelerated fibrinogen catabolism suggested increased intravascular degradation. Obviously, the impaired balance was still compensated since no evidence for organ deposition of fibrin was found. However, additional trigger mechanisms, which individually are not thrombogenic in the normal rat – hypercalcaemia and bacterial endotoxins – led to the development of thrombotic conditions in tumour bearing rats resulting in microangiopathic haemolytic anaemia or in the generalized Shwartzman reaction. Preventive anticoagulation was only effective if established prior to the second stimulus. In addition, the experiments suggested that rapid decomposition of tumour cells, disturbances in the functional state of the reticuloendothelial system, a decreased fibrinolytic potential and, possibly, leukocytosis are supplementary predisposing factors to thrombosis in malignant diseases. It is concluded that the low grade activation of the clotting mechanism in experimental cancer respresents the “hpyercoagulable state” which is at high risk to be converted into a thrombotic state.* Supported by the “Deutsche Forschungsgemeinschaft”, Bonn-Bad Godesberg.

scholarly journals HOST-PARASITE FACTORS IN GROUP A STREPTOCOCCAL INFECTIONS

1960 ◽  
Vol 111 (2) ◽  
pp. 255-284 ◽  
Author(s):  
Dennis W. Watson
Keyword(s):  
Scarlet Fever ◽  
Intravenous Injections ◽  
Streptolysin O ◽  
Bacterial Endotoxins ◽  
Group A ◽  
Shwartzman Reaction ◽  
Host Parasite ◽  
Parasite Factors ◽  
Pyrogenic Activity

The factors present in streptococcal lesion extracts (SLE) which enhanced the lethal and tissue-damaging properties of Gram-negative bacterial endotoxins and streptolysin O were identified with the scarlet fever group of toxins. Toxic manifestations attributed to this group of toxins included lethality, cardiotoxic and other tissue damage, enhancement of toxicity, and pyrogenicity. Of these, the measurement of febrile response in American Dutch rabbits was the most useful parameter of toxicity. In rabbits, repeated daily intravenous injections of 0.125 Lf of a purified erythrogenic toxin immunizes specifically against the pyrogenic activity; this technique was used to type the toxins and to distinguish them from exogenous and endogenous pyrogens; non-specific pyrogens, such as streptococcal endotoxin, were not found in SLE. All types of the Lancefield Group A streptococci tested produced one or or more immunologically distinct toxins in vivo in contrast to Groups B and C which did not produce them; toxins A and B, previously distinguished by neutralization of rash-inducing activity in the skin, were produced in vivo. The A toxin was the most common, as indicated by its presence in extracts prepared with Types 28, 12, 17, and 10 (NY-5); B toxin was found in 10 (NY-5) and 19. A new toxin, designated C, was obtained from a Type 18. In American Dutch rabbits, purified toxin at a concentration of 15 Lf (900,000 STD) neither gave a Dick test nor prepared the skin for the local Shwartzman reaction; by this route, however, in contrast to classical endotoxins, they enhance the lethal and tissue-damaging properties of sublethal doses of these and other toxins. These properties of the immunologic distinct exotoxins as demonstrated in American Dutch rabbits suggest by analogy their importance in the pathogenesis of streptococcal disease in man. Evidence that might implicate them in sequelae, in addition to scarlet fever, is discussed.

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