scholarly journals STUDIES OF THE EFFECT OF BACTERIAL ENDOTOXINS ON RABBIT LEUCOCYTES

1953 ◽  
Vol 98 (4) ◽  
pp. 349-364 ◽  
Author(s):  
Leighton E. Cluff
Keyword(s):  
Buffy Coat ◽  
Development Of Resistance ◽  
Bacterial Endotoxins ◽  
Leucocyte Migration ◽  
Shwartzman Reaction ◽  
Rapid Removal ◽  
And Migration ◽  
Shwartzman Phenomenon ◽  
Reticulo Endothelial System ◽  
Development Of Tolerance

Bacterial endotoxin injected intravenously into rabbits inhibited the migration of leucocytes from the buffy coat of centrifuged blood (4). Repeated daily injections of endotoxin resulted in the rabbits becoming resistant to the fever-inducing action of the toxin, and migration of leucocytes from centrifuged blood was no longer inhibited by injection of the toxin. Leucocyte migration from the buffy coat of centrifuged blood after injection of toxin into the rabbits appeared gradually over the first few days of repeated injections, and disappeared during the 10 to 15 days after cessation of daily injections of toxin. The resistance to endotoxin, demonstrated by leucocyte migration and pyrogen tolerance, could not be passively transferred with serum from resistant animals, and was non-specific, in that resistance to one endotoxin conferred some resistance to toxin from an organism of a different species. No relationship could be demonstrated between precipitin titer and resistance. Thorotrast abolished resistance to the fever-inducing activity of endotoxin, but its effect on leucocyte resistance was not clear, since when injected alone it inhibited migration of leucocytes from the buffy coat of centrifuged blood. The suggestion is made that the failure of toxin to inhibit the migration of leucocytes from resistant rabbits is due either to the presence of leucocytes which have become adapted to the toxin by repeated exposure, or to rapid removal of the toxin by the reticulo-endothelial system. It is unlikely that leucocyte resistance participates in the development of tolerance to the fever-inducing action of endotoxin. However, in view of the participation of the leucocyte in the pathogenesis of the Shwartzman reaction, the presence of leucocytes resistant to endotoxin may be responsible in part for the development of resistance to the Shwartzman phenomenon.

scholarly journals STUDIES OF THE EFFECT OF BACTERIAL ENDOTOXINS ON RABBIT LEUCOCYTES

1953 ◽  
Vol 98 (4) ◽  
pp. 331-348 ◽  
Author(s):  
Morgan Berthrong ◽  
Leighton E. Cluff
Keyword(s):  
Intravenous Injection ◽  
Inhibitory Effect ◽  
Buffy Coat ◽  
Single Intravenous Injection ◽  
Bacterial Endotoxins ◽  
Leucocyte Migration ◽  
Shwartzman Reaction ◽  
Local Shwartzman Reaction

Intravenous injection into rabbits of bacterial endotoxins results in an inhibition of migration of leucocytes from the buffy coat of their blood in tissue culture or in "slide cell" preparations. This effect was demonstrable 5 minutes after the intravenous injection and persisted for from 6 to 12 hours after the injection. It is as marked in rabbits receiving only a single intravenous injection of endotoxin as in those previously prepared intradermally and developing a severe local Shwartzman reaction on intravenous injection. The preparation of the skin for the Shwartzman reaction does not in itself result in appreciable changes of leucocyte migration. The production of the effect depends upon some action in vivo, since leucocytes of uninjected rabbits migrate normally from the buffy coat in plasma substrates to which large concentrations of endotoxin are added in vitro. The inhibitory effect, as observed in these experiments, also depends upon the added influence of centrifugation. Leucocytes from a rabbit receiving endotoxin intravenously migrate normally from uncentrifuged lung or spleen fragments and migrate normally in blood on the warm stage prior to centrifugation. Identical centrifugation does not affect leucocytes from uninjected animals. The heparin inhibition of the local Shwartzman reaction does not alter this effect of endotoxins on leucocytes. Its possible role in the production of leucopenia and of the local Shwartzman reaction is briefly discussed.

scholarly journals THE RELATIONSHIP BETWEEN THE VASCULAR MANIFESTATIONS OF SHOCK PRODUCED BY ENDOTOXIN, TRAUMA, AND HEMORRHAGE

1957 ◽  
Vol 106 (3) ◽  
pp. 403-414 ◽  
Author(s):  
Benjamin W. Zweifach ◽  
Baruj Benacerraf ◽  
Lewis Thomas ◽  
Keyword(s):  
Traumatic Shock ◽  
Cross Tolerance ◽  
Vascular Effects ◽  
Phagocytic Capacity ◽  
E Coli ◽  
Development Of Resistance ◽  
Bacterial Endotoxins ◽  
Induced Tolerance ◽  
The Relationship ◽  
Reticulo Endothelial System

In studies designed to establish the interrelationship between bacterial endotoxins and the vascular sequelae of hemorrhagic and traumatic shock, the effect of factors known to influence the phagocytic behavior of the reticulo-endothelial system (RES) were investigated. Measures which induced a so called "blockade" of the RES were uniformly associated with an exacerbation of the vascular effects of the endotoxin of E. coli. Such pretreatment also counteracted the cross-tolerance induced by endotoxins against the lethal effects of hemorrhage or drum trauma. The vascular reactions characteristic of irreversible hemorrhagic shock could be simulated by a combination of pretreatment with carbon or proferrin and the infusion of small doses of E. coli endotoxin. An increase in the phagocytic activity of the RES, induced by repeated injections of certain colloids, was associated with an enhanced tolerance of shock. Measurement of carbon clearance values indicated that although an augmented phagocytic capacity was present in rats with induced tolerance to bacterial endotoxins, the development of resistance to trauma was not associated with a comparable change in the phagocytic function of the RES.

scholarly journals PATHOGENESIS OF EXPERIMENTAL SHOCK

1961 ◽  
Vol 114 (2) ◽  
pp. 195-204 ◽  
Author(s):  
Arnold L. Nagler ◽  
Benjamin W. Zweifach
Keyword(s):  
Hemorrhagic Shock ◽  
Passive Transfer ◽  
Skin Reactions ◽  
Positive Skin ◽  
E Coli ◽  
Bacterial Endotoxins ◽  
Experimental Shock ◽  
Test Reactions ◽  
Shwartzman Reaction ◽  
Shwartzman Phenomenon

A series of biological test reactions was used in order to establish the presence of bacterial endotoxins in the blood of rabbits during the progression of hemorrhagic shock. 1. When the shocked animal was used as the test object, it was not possible to induce either the generalized Shwartzman reaction or the dermal Shwartzman phenomenon with exogenous endotoxin (S. enteritidis or E. coli) as one of the two provocative factors. 2. Epinephrine instilled into the skin of rabbits either before, during, or after an episode of hemorrhagic shock did not result in the hemorrhagic skin reaction which occurs in the presence of as little as 1 µg of endotoxin intravenously. 3. Passive transfer from a donor in the irreversible phase of shock of 20 to 25 ml of blood into a primed recipient (B.P. at 40 mm Hg for 1 hour) was uniformly lethal. 4. Similar amounts of blood from such shocked donor failed upon intravenous injection to elicit a protective hemorrhagic reaction in skin sites which were infiltrated with 100 µg of epinephrine. In the same animals 1 µg of endotoxin added to the blood samples caused a positive dermal response. 5. Blood was taken from rabbits which had been pretreated with S. enteritidis endotoxin and then subjected to hemorrhagic shock (35 mm Hg for 2 hours). Such samples upon passive transfer produced positive skin reactions in epinephrine sites but were not lethal to the primed test recipient used in these studies. It is concluded that the contribution of bacterial endotoxemia to the genesis of hemorrhagic shock remains to be determined.

scholarly journals Expression of wild-type and mutated rabbit osteopontin in Escherichia coli, and their effects on adhesion and migration of P388D1 cells

1995 ◽  
Vol 307 (1) ◽  
pp. 257-265 ◽  
Author(s):  
K Nasu ◽  
T Ishida ◽  
M Setoguchi ◽  
Y Higuchi ◽  
S Akizuki ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Fluid Phase ◽  
Intradermal Injection ◽  
Polymorphonuclear Leucocyte ◽  
Alpha Subunit ◽  
Wild Type ◽  
Alpha Subunits ◽  
Leucocyte Migration ◽  
And Migration ◽  
Chemotactic Effect

Recombinant wild-type rabbit osteopontin (rOP) and the protein with an aspartate-to-glutamate transposition induced by a point mutation in the rabbit OP cDNA within the Gly-Arg-Gly-Asp-Ser (GRGDS) sequence were expressed in Escherichia coli and purified to homogeneity. P388D1 cells bound rOP in a saturable manner. rOP induced adhesion and haptotaxis of P388D1 cells, whereas mutated rabbit OP (rOPmut) did not. Anti-rOP IgG F(ab′)2 and synthetic GRGDS peptide inhibited rOP-mediated adhesion and haptotaxis of P388D1 cells. Fibronectin (FN)-mediated adhesion of P388D1 cells was markedly inhibited in the presence of fluid-phase rOP. Adhesion of P388D1 cells to rOP was significantly inhibited by anti-[alpha-subunits of VLA4 (alpha 4) and VLA5 (alpha 5)] monoclonal antibodies (mAbs), but not by anti-[alpha-subunit of vitronectin (VN) receptor (alpha V) or Mac-1 (alpha M)] mAb. Adhesion of P388D1 cells to FN and VN was significantly inhibited by anti-alpha V mAb but not anti-alpha 4, -alpha 5 or -alpha M mAb. Haptotaxis of P388D1 cells to rOP was significantly inhibited by anti-alpha V mAb, but not by anti-alpha 4, -alpha 5 and alpha M mAbs, whereas that to FN showed no inhibition with all three mAbs. Haptotaxis of P388D1 cells to VN was significantly inhibited by anti-alpha 5 and -alpha V mAbs but not by anti-alpha 4 and -alpha M mAbs. Similar features of inhibition of adhesion and haptotaxis of P388D1 cells to human OP were observed by mAbs. rOP had no chemotactic effect on P388D1 cells. Significant polymorphonuclear leucocyte migration was observed 3-12 h after intradermal injection of rOP into rabbits.

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.

An Appraisal of Fulminant Meningococcemia with Reference to the Shwartzman Phenomenon

PEDIATRICS ◽  
1959 ◽  
Vol 23 (2) ◽  
pp. 341-341
Keyword(s):  
Steroid Therapy ◽  
Special Interest ◽  
Primary Lesion ◽  
Adrenal Steroids ◽  
Cortical Necrosis ◽  
Vascular Thrombosis ◽  
Adrenal Steroid ◽  
Shwartzman Reaction ◽  
Time Of Admission ◽  
Shwartzman Phenomenon

The object of this study was to evaluate the evidence for and against operation of the Shwartzman phenomenon (local or generalized) in meningococcemia. It is based on 52 cases of meningococcus infection seen at the Cincinnati Children's Hospital in a 20 year period. The fatal cases were compared with 152 patients who survived meningococcus infection. Vascular thrombosis appears to be the primary lesion involved in the production of the hemorrhagic lesions of the skin and adrenals in acute meningococcemia. It is suggested that these lesions may be produced by a local Shwartzman phenomenon. Of special interest is the occurrence of three instances of renal cortical necrosis, such as is seen characteristically in the generalized Shwartzman reaction. Because of the similarity of the lesions found in the fatal cases of meningococcus infection with the Shwartzman phenomenon, and the fact that cortisone is one of the most efficient methods of potentiating the Shwartzman phenomenon, led the authors to question the wisdom of the use of adrenal steroid therapy in fulminating meningococcus septicemia. It was also found that of 156 patients with meningococcus infection, not in shock at the time of admission, there was a mortality of 21% for the patients who received adrenal steroid therapy compared with a 7% mortality in those who did not receive adrenal steroids.

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 PLATELETS AND THE SHWARTZMAN PHENOMENON

1965 ◽  
Vol 121 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Jack Levin ◽  
Leighton E. Cluff
Keyword(s):  
Intravenous Injection ◽  
Renal Lesions ◽  
Shwartzman Reaction ◽  
Hemorrhagic Lesion ◽  
Shwartzman Phenomenon

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.

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.

Resistance to whole-body X-irradiation in rats made tolerant to bacterial endotoxins

1959 ◽  
Vol 197 (6) ◽  
pp. 1364-1370 ◽  
Author(s):  
B. W. Zweifach ◽  
E. Kivy-Rosenberg ◽  
Arnold L. Nagler
Keyword(s):  
Blood Platelet ◽  
Reticuloendothelial System ◽  
Whole Body ◽  
X Rays ◽  
Effective Protection ◽  
X Ray ◽  
E Coli ◽  
Bacterial Endotoxins ◽  
X Irradiation ◽  
Reticulo Endothelial System

Rats were treated with three conditioning agents (bacterial endotoxins, zymosan and compound 48/80) known to produce tolerance to other forms of stress, as a means of determining the importance of the reticulo-endothelial system in the response to WBR. Effective protection was provided by tolerance induced by lipopolysaccharide extracts of E. coli bacteria. Some protection was also afforded by conditioning with 48/80 for several days. These agents were active only when administered before exposure to x-rays. Treatment post x-ray broke down the induced resistance. Blood platelet levels remained high in conditioned animals exposed to WBR. It is suggested that a relationship exists between the priming or conditioning of the reticuloendothelial system and the maintenance of satisfactory blood platelet levels in adapted animals receiving WBR.

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