Vessel Wall and Thrombogenesis - Endotoxin

1973 ◽  
Vol 29 (01) ◽  
pp. 011-026 ◽  
Author(s):  
Donald G McKay

SummaryThe generalized Shwartzman reaction is a definitive disease process which is the result of two minor episodes of acute inflammation of the circulating blood. The identifying feature of the reaction is thrombosis of the micro circulation, specifically of glomerular capillary thrombosis which persists long enough to cause bilateral renal cortical necrosis. The reaction is the result of an interplay between leukocytes, platelets, complement, the contact system, the extrinsic prothrombin activator system, adrenal glucocorticoids, adrenal catecholamines, alpha - adrenergic receptor sites and the fibrinolytic enzyme system. The reaction occurs only when these systems are affected within narrow quantitative limits. It is a model of the effects of bacterial endotoxin on the blood-vascular system and has important implications for acute inflammatory episodes of the circulating blood induced by other inflammatory agents such as antigen-antibody complex and particulate matter.

1963 ◽  
Vol 117 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Leung Lee

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.


1971 ◽  
Vol 26 (01) ◽  
pp. 071-076 ◽  
Author(s):  
D.G McKay ◽  
J.-G Latour ◽  
Anatalia M. Lopez

SummaryInfusion of activated purified Hageman factor and norepinephrine into pregnant rats produces renal glomerular capillary thrombosis identical to the generalized Shwartzman reaction. Activated Hageman factor alone, norepinephrine alone, and inosithin (a substitute for platelet phospholipid) alone, in addition to the combination of inosithin and norepinephrine were incapable of causing the reaction. These studies confirm the evidence that four basic components of the reaction are 1. activation of Hageman factor, 2. platelet phospholipid, 3. ‘‘fibrinolysin inhibition’’, and 4. stimulation of α-adrenergic receptor sites.


Author(s):  
William P. Jollie

A technique has been developed for visualizing antibody against horseradish peroxidase (HRP) in rat visceral yolk sac, the placental membrane across which passive immunity previously has been shown to be transferred from mother to young just prior to birth. Female rats were immunized by injecting both hind foot pads with 1 mg HRP emulsified in complete Freund's adjuvant. They were given a booster of 0.5mg HRP in 0.1 ml normal saline i.v. after one week, then bred and autopsied at selected stages of pregnancy, viz., 12, 1 7 and 22 days post coitum, receiving a second booster, injected as above, five days before autopsy. Yolk sacs were removed surgically and fixed immediately in 2% paraformaldehye, 1% glutaraldehye in 0.1 M phosphate buffer with 0.01% CaCl2 at pH 7.4, room temperature, for 3 hr, rinsed 3X in 0.1 M phosphate buffer plus 5% sucrose, then exposed to 1 mg HRP in 1 ml 0.1 M phosphate buffer at pH 7.4 for 1 hr. They were refixed in aldehydes, as above, for 1 5 min (to assure binding of antigen-antibody complex). Following buffer washes, the tissues were incubated in 3 mg diaminobenzidine tetrahydrochloride and 0.01% H2O2 in 0.05 M Tris-HCl buffer for 30 min. After brief buffer washes, they were postfixed in 2% OsO4. in phosphate buffer at pH 7.4, 4°C for 2 hr, dehydrated through a graded series of ethanols, and embedded in Durcupan. Thin sections were observed and photographed without contrast-enhancement with heavy metals. Cytochemical reaction product marked the site of HRP (i.e., antigen) which, in turn, was present only where it was bound with anti-HRP antibody.


1970 ◽  
Vol 23 (03) ◽  
pp. 417-422 ◽  
Author(s):  
D. G McKay ◽  
J.-G Latour ◽  
Mary H. Parrish

SummaryThe infusion of epinephrine in high doses produces disseminated intravascular coagulation by activation of Hageman factor. The effect is blocked by phenoxybenz-amine and is therefore due to stimulation of α-adrenergic receptor sites.


1964 ◽  
Vol 12 (02) ◽  
pp. 462-470 ◽  
Author(s):  
F Rodríguez-Erdmann

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.


1966 ◽  
Vol 51 (1) ◽  
pp. 88-94 ◽  
Author(s):  
A. Villanueva ◽  
S. J. H. Ashcroft ◽  
J. P. Felber

ABSTRACT The synthetic ACTH peptides β1–39 and β1–24 stimulated lipolysis as determined by the rat epididymal fat pad in vitro. The stimulating effect of these peptides was diminished by prior incubation of the peptides with antibodies produced by the guinea-pig against ACTH. The stimulating effect of these hormones was also diminished by the double antibody system used in the radio-immunoassay of ACTH and other peptide hormones, in which incubation with antiserum is followed by precipitation of the antigen-antibody complex by rabbit anti-guinea-pig-γ-globulin.


1973 ◽  
Vol 71 (4_Suppl) ◽  
pp. S11
Author(s):  
K. Schemmel ◽  
L. Weisbecker ◽  
H. Norden ◽  
V. Mokmol ◽  
V. Becker ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Semra Zuhal Birol ◽  
Rana Fucucuoglu ◽  
Sertac Cadirci ◽  
Ayca Sayi-Yazgan ◽  
Levent Trabzon

AbstractAtherosclerosis is a long-term disease process of the vascular system that is characterized by the formation of atherosclerotic plaques, which are inflammatory regions on medium and large-sized arteries. There are many factors contributing to plaque formation, such as changes in shear stress levels, rupture of endothelial cells, accumulation of lipids, and recruitment of leukocytes. Shear stress is one of the main factors that regulates the homeostasis of the circulatory system; therefore, sudden and chronic changes in shear stress may cause severe pathological conditions. In this study, microfluidic channels with cavitations were designed to mimic the shape of the atherosclerotic blood vessel, where the shear stress and pressure difference depend on design of the microchannels. Changes in the inflammatory-related molecules ICAM-1 and IL-8 were investigated in THP-1 cells in response to applied shear stresses in an continuous cycling system through microfluidic channels with periodic cavitations. ICAM-1 mRNA expression and IL-8 release were analyzed by qRT-PCR and ELISA, respectively. Additionally, the adhesion behavior of sheared THP-1 cells to endothelial cells was examined by fluorescence microscopy. The results showed that 15 Pa shear stress significantly increases expression of ICAM-1 gene and IL-8 release in THP-1 cells, whereas it decreases the adhesion between THP-1 cells and endothelial cells.


Sign in / Sign up

Export Citation Format

Share Document