scholarly journals ANTIGEN-ANTIBODY REACTION IN THE PATHOGENESIS OF BILATERAL RENAL CORTICAL NECROSIS

1963 ◽  
Vol 117 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Leung Lee
Keyword(s):  
Immune Complexes ◽  
Coagulation System ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Soluble Immune Complexes ◽  
Antigen Antibody ◽  
Glomerular Capillaries

In the presence of reticuloendothelial blockade, the intravenous injection of a protein antigen into specifically immunized rabbits or the infusion of soluble immune complexes into normal animals has been shown to result in the production of bilateral renal cortical necrosis. The similarity in the pathogenesis of this lesion and that seen in the classical generalized Shwartzman reaction produced by bacterial endotoxins is indicated by (a) the failure of both lesions to develop in animals pretreated with large doses of heparin, (b) by the finding of "heparin-precipitable fibrinogen" in the circulation, and (c) by the presence of massive fibrin deposits within the glomerular capillaries. These findings indicate that antigen-antibody reactions in vivo are capable of activating the blood coagulation system and that the mode of action of bacterial endotoxins may have an immunological basis.

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 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 Intravascular Coagulation with Generalized Shwartzman Reaction Induced by a Heparin-Like Anticoagulant (Liquoid)

1967 ◽  
Vol 18 (01/02) ◽  
pp. 024-039 ◽  
Author(s):  
S. A Evensen ◽  
M Jeremic ◽  
P. F Hjort
Keyword(s):  
Body Weight ◽  
Intravenous Injection ◽  
Anticoagulant Effect ◽  
Coagulation System ◽  
Factor V ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Intravascular Coagulation ◽  
Shwartzman Reaction

SummaryLiquoid (sodium polyanethol sulfonate), a synthetic heparin-like anticoagulant, produces renal cortical necrosis in rabbits. This lesion is indistinguishable from the generalized Shwartzman reaction which is caused by intravascular coagulation in a prepared animal. We have investigated this apparently paradoxic effect of Liquoid. Our main findings are:1. Liquoid is a potent heparin-like anticoagulant. One mg of Liquoid is neutralized by 1 mg of Polybrene. After intravenous injection the anticoagulant effect is immediate and persists for several hours.2. In larger concentrations, Liquoid precipitates fibrinogen. The precipitation does not depend on an intact coagulation system; the precipitates are dissolved in 30% urea.3. An intravenous injection of 20 mg Liquoid/1500 g body-weight produces an early thrombocytopenia, a progressive depletion of fibrinogen and factor V, the appearance of cold-precipitating material in plasma, and severe renal cortical necrosis.4. Pretreatment with warfarin completely prevents all of these effects, except a moderate fall in platelets.We conclude that Liquoid produces these effects, not by precipitation of fibrinogen, but by intravascular coagulation, probably released through aggregation and damage of the platelets. Thus, intravascular coagulation is again confirmed as the final event in the generalized Shwartzman reaction.

Effect of Anticoagulating and Non-Anticoagulating Concentrations of Heparin on the Generalized Shwartzman Reaction

1970 ◽  
Vol 24 (01/02) ◽  
pp. 136-145 ◽  
Author(s):  
J. J Corrigan
Keyword(s):  
Dose Group ◽  
Blood Platelets ◽  
Coagulation Factors ◽  
Renal Lesion ◽  
Fibrin Deposition ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Intravenous Injections ◽  
Shwartzman Reaction

SummaryRabbits given 2 properly spaced intravenous injections of bacterial endotoxin develop bilateral renal cortical necrosis (generalized Shwartzman reaction - gSr). This renal lesion is the result of fibrin deposition secondary to diffuse intravascular clotting (DIC). Using this experimental model, the effect of anticoagulating (large) and non- anticoagulating (small) concentrations of heparin on the changes in blood platelets, plasma coagulation factors II, V, VIII and fibrinogen during the production of renal cortical necrosis was studied. The data demonstrate that all amounts of heparin given during, but not after, the period of intravascular clotting reduced the frequency of renal cortical necrosis. Anticoagulating concentrations completely prevented the renal lesion. Non-anticoagulating amounts could reduce the frequency of the renal lesions, but this effect was not predictable or consistent. Coagulation studies in the large dose group revealed thrombocytopenia reduced factors II, V, and VIII but no fibrinogen consumption. These findings suggest that heparin inhibits the formation of fibrin in vivo, thereby preventing the formation of renal cortical necrosis. The coagulation data in the small dose group differed in that fibrinogen consumption did occur. The possible explanations for the phenomenon were discussed.

Studies on the Pathogenesis of the Generalized Shwartzman Reaction

1964 ◽  
Vol 12 (02) ◽  
pp. 462-470 ◽  
Author(s):  
F Rodríguez-Erdmann
Keyword(s):  
Fibrinolytic System ◽  
Factor V ◽  
Morphological Pattern ◽  
Cortical Necrosis ◽  
G Factor ◽  
Conventional Form ◽  
Renal Cortical Necrosis ◽  
Shwartzman Reaction

SummaryAnimals treated in the conventional form to elicit the generalized Shwartzman reaction (gSr) by means of properly spaced injections of endotoxin develop an abrupt consumption of the plasmatic factors of the clotting mechanism, as demonstrated by the reduction of the activity of prothrombin and Ac-G (factor V). These animals show ultimatly characteristic morphological pattern: bilateral cortical necrosis of the kidney. Rabbits treated four hours after the second (‘‘provocative”) endotoxin injection with streptokinase (Varidase/Lederle) in order to activate the fibrinolytic system failed to develop the renal cortical necrosis, but their prothrombin and Ac-G (factor V) level decreased abruptly.Through indirect deduction the intravascular presence of thrombin-like activity is accepted four hours after the “provocative” endotoxin injection.

scholarly journals The Generalized Shwartzman Reaction and Haemophilus Infections in Pigs

1967 ◽  
Vol 4 (3) ◽  
pp. 245-253 ◽  
Author(s):  
K. Nordstoga ◽  
M. Fj⊘lstad
Keyword(s):  
Bacterial Endotoxin ◽  
Vascular Lesions ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Haemophilus Parainfluenzae ◽  
Shwartzman Reaction ◽  
Fibrinoid Degeneration

Four pigs were injected intravenously twice at a 24-hour interval with disintegrated cells of Haemophilus parainfluenzae and killed 24 h later. Two of the pigs developed bilateral renal cortical necrosis (BCN) and renal and extrarenal vascular lesions characterized by fibrinous thrombosis and fibrinoid degeneration. The BCN is interpreted as being the result of a generalized Shwartzman reaction to bacterial endotoxin. The experiment supports the view that the vascular lesions accompanying outbreaks of Haemophilus infections in swine are due to a generalized Shwartzman reaction.

FATE OF PREFORMED IMMUNE COMPLEXES IN RABBITS AND RHESUS MONKEYS

1971 ◽  
Vol 134 (3) ◽  
pp. 19-31 ◽  
Author(s):  
Mart Mannik ◽  
William P. Arend
Keyword(s):  
Immune Complexes ◽  
Rhesus Monkeys ◽  
Hepatic Uptake ◽  
In Vivo Studies ◽  
Complement Components ◽  
Immune Adherence ◽  
Soluble Immune Complexes ◽  
Lattice Formation

Preformed soluble immune complexes injected into rabbits or rhesus monkeys showed similar characteristics of disappearance from circulation. Complexes made with intact γG-antibodies and exceeding the Ag2Ab2 lattice formation were rapidly removed by the hepatic RES. These complexes fixed complement effectively in vitro. Their hepatic uptake was not dependent upon circulating complement components, since their accumulation in the liver was unchanged in complement depleted rabbits. Similar antigen-antibody complexes made with reduced and alkylated γG-antibodies fixed complement ineffectively in vitro. These complexes possessed different disappearance characteristics and were not rapidly taken up by the liver, regardless of their degree of lattice formation. Both in vitro and in vivo studies failed to suggest any role for the immune adherence receptor on primate erythrocytes in the handling of circulating soluble immune complexes composed of BSA and γG-antibodies to this antigen.

Prevention Of Shwartzman’S Phenomenon In Factor XIII Deficiency

1981 ◽  
Author(s):  
Soo Young Lee ◽  
Sung Keun Chang ◽  
Soo II Chung
Keyword(s):  
Factor Xiii ◽  
Rabbit Platelet ◽  
Factor Xiii Deficiency ◽  
Platelet Factor ◽  
Cortical Necrosis ◽  
Rate Of Increase ◽  
Shwartzman Reaction

Cross-linked clots formed in vitro are reported to be more resistant to fibrinolysis but the relevance of these observations to the situation in vivo is uncertain. The possible role of Factor XIII in the formation of diffuse intravascular fibrin deposition was examined in experimentally induced Factor XIII deficient rabbits. Factor XIII deficiency was induced by intravenous infusion of IgG isolated from goat anti-rabbit platelet Factor XIII. Control received normal goat IgG. The Shwartzman reaction was produced by two injections of bacterial endotoxin given 24 hours apart.The most striking histological differences were observed after 48 hours. A large number of glomerular loops were enlarged and engorged with red blood cells and platelet- fibrin thrombi; extensive bilateral cortical necrosis was observed in 8 out of 10 endotoxin injected control rabbits but none in the Factor XIII deficient group.Fibrinogen levels in control rabbits were increased 3-4 fold (1.1g/100 ml), at 24 hours and slightly decreased at 48 hours after endotoxin injection, whereas in Factor XIII deficient animals, the rate of increase was slower but reached similar levels at 48 hours. Fibrinolytic activity in vivo, studied by the degradation of infused 125I-fibrinogen, was significantly increased in both endotoxin injected groups, irrespective of Factor XIII levels.These results strongly suggest that cross-linked thrombi are more resistant to fibrinolysis in vivo as well as in vitro.

scholarly journals A cell-mediated reaction against glomerular-bound immune complexes.

1979 ◽  
Vol 150 (6) ◽  
pp. 1410-1420 ◽  
Author(s):  
A K Bhan ◽  
A B Collins ◽  
E E Schneeberger ◽  
R T McCluskey
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Immune Complexes ◽  
Gamma Globulin ◽  
Mononuclear Phagocytes ◽  
A Cell ◽  
Lymph Node Cells ◽  
Soluble Immune Complexes ◽  
Histologic Changes ◽  
Glomerular Capillaries

Lewis rats were given a single i.v. injection of soluble immune complexes containing human serum albumin (HSA) and rabbit anti-HSA antibodies, prepared in antigen excess. This resulted in localization of HSA and rabbit gamma globulin (RGG) in glomerular mesangial regions without producing definite histologic changes. 24 h after the injection of immune complexes, groups of these rats received lymph node cells or T-cell preparations from syngeneic donors sensitized to RGG, HSA, or ovalbumin; another group received no cells. All of these groups and a group of normal control rats were given injections of [3H]thymidine at 18, 27, and 44 h. The animals were killed 48 h after the time of cell transfer. In histologic sections, glomerular abnormalities were found only in some of the animals that had received immune complexes and lymph node cells or T-cell populations from donors sensitized to HSA or RGG; the lesions were characterized by focal and segmental increase in cells in mesangial regions. Autoradiographs revealed significantly greater numbers of labeled cells in mesangial regions and glomerular capillaries in the groups that had received immune complexes and cells from HSA- or RGG-sensitized donors than in any of the other groups. Electronmicroscopic studies suggested that the increase in cellularity in mesangial regions resulted from an influx of mononuclear phagocytes. The findings indicate that cell-mediated reactions can be initiated by the interaction between sensitized T lymphocytes and antigens present in immune complexes within mesangial regions.

scholarly journals Endocytosis of soluble immune complexes leads to their clearance by FcγRIIIB but induces neutrophil extracellular traps via FcγRIIA in vivo

Blood ◽  
2012 ◽  
Vol 120 (22) ◽  
pp. 4421-4431 ◽  
Author(s):  
Kan Chen ◽  
Hiroshi Nishi ◽  
Richard Travers ◽  
Naotake Tsuboi ◽  
Kimberly Martinod ◽  
...  
Keyword(s):  
Immune Complexes ◽  
Fluid Phase ◽  
Neutrophil Extracellular Traps ◽  
Humoral Factors ◽  
Extracellular Traps ◽  
Fluid Phase Endocytosis ◽  
Soluble Immune Complexes ◽  
The Individual

Abstract Soluble immune complexes (ICs) are abundant in autoimmune diseases, yet neutrophil responses to these soluble humoral factors remain uncharacterized. Moreover, the individual role of the uniquely human FcγRIIA and glycophosphatidylinositol (GPI)–linked FcγRIIIB in IC-mediated inflammation is still debated. Here we exploited mice and cell lines expressing these human neutrophil FcγRs to demonstrate that FcγRIIIB alone, in the absence of its known signaling partners FcγRIIA and the integrin Mac-1, internalizes soluble ICs through a mechanism used by GPI-anchored receptors and fluid-phase endocytosis. FcγRIIA also uses this pathway. As shown by intravital microscopy, FcγRIIA but not FcγRIIIB-mediated neutrophil interactions with extravascular soluble ICs results in the formation of neutrophil extracellular traps (NETs) in tissues. Unexpectedly, in wild-type mice, IC-induced NETosis does not rely on the NADPH oxidase, myeloperoxidase, or neutrophil elastase. In the context of soluble ICs present primarily within vessels, FcγRIIIB-mediated neutrophil recruitment requires Mac-1 and is associated with the removal of intravascular IC deposits. Collectively, our studies assign a new role for FcγRIIIB in the removal of soluble ICs within the vasculature that may serve to maintain homeostasis, whereas FcγRIIA engagement of tissue soluble ICs generates NETs, a proinflammatory process linked to autoimmunity.

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