Inactivation of Endotoxin by a Humoral Component

Landy, Maurice; Trapani, Robert-John; Shear, M. J.

doi:10.1084/jem.110.5.731

Cited by 10 publications

(7 citation statements)

References 13 publications

(12 reference statements)

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“…The Serratia marcescens endotoxin supplied by Dr. Landy is highly purified, as judged by its low nitrogen content, but is no more toxic than the acetone-ether-dried S. typhimurium, as indicated by the data of Table V. This same material, according to Landy et al (13)(14)(15)(16), is a potent pyrogen, however, and is effective in tumor necrosis. The Upjohn preparation of E. coli lipopolysaccharide stands out, on the other hand, as the most active material so far tested by the urinary nitrogen assay and is unusually lethal for mice.…”

Section: Effect Of E Coli Lipopolysaccharide O~ Nitrogen Excretion Fmentioning

confidence: 95%

“…Influence of Serum "Endotoxin-Detoxifying Component" (EDC) and DCI on the Assay for E. coli Endotoxin.--As Landy and collaborators have reported in a series of publications (13)(14)(15)(16), calcium-free serum from a number of animal sources is capable of detoxifying endotoxin as judged by its loss of (a) tumornecrotizing action, (b) toxicity for experimental animals, and (c) antigenicity. With this work as a background, the effect of calcium-free mouse serum on Table IV were obtained.…”

Section: Effect Of E Coli Lipopolysaccharide O~ Nitrogen Excretion Fmentioning

confidence: 99%

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Effects of Bacterial Endotoxins on Metabolism

Berry

Smythe

1961

The Journal of Experimental Medicine

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Endotoxins can be assayed on the basis of their toxicity for experimental animals, their pyrogenicity, their ability to necrotize tumors, and their antigenicity. Another property, observed in the course of recent experiments, makes possible a new assay. The initial observation on which the assay is based was obtained when an intraperitoneal injection of appropriate numbers of heatkilled cells of Salmonella typhimurium was found to prevent completely the elevation in urinary nitrogen excreted by mice given adrenocorticotropic hormone (ACTH) subcutaneously (1). The same number of heat-killed cells had no apparent effect on the total protein catabolized in response to concurrently injected cortisone as judged by the increase in urinary nitrogen eliminated under these conditions. From these observations, endotoxins seem to prevent certain physiological manifestations normally elicited by ACTH but do not influence the metabolic activity of exogenous glycocorticoid. Since there is an inverse proportionality between the quantity of endotoxin injected and the quantity of urinary nitrogen excreted following ACTH administration (2), this relationship has been used to develop the assay. In order to establish the validity of such an assay, endotoxin alone must be shown to produce the effect on which the assay is based. The extent to which such proof is possible is, of course, limited but within these limits the evidence to be presented is convincing. It is also necessary to determine the sensitivity of the assay before its usefulness can be related to other methods. This report is concerned with results obtained with these aims in mind. Method•ndotoadn.--Seven different preparations were used. A saline suspension of a known number of Salmonella typhimur~um, strain SR-11, were killed by pasteurization at 60°C.for 30 minutes. Lack of growth on subculture in brain-heart infusion broth (Difco) was taken as proof of steAlization. Usually the suspension had to be heated a second or third time before no growth was observed. The final material was stored at 5°C. in sealed vials. The dry weight of three different preparations was found to be about 8/~ mg. per 109 heat-killed cells. Comparatively crude endotoxin was derived as acetone and ether-extracted cells of

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Section: Effect Of E Coli Lipopolysaccharide O~ Nitrogen Excretion Fmentioning

confidence: 95%

Section: Effect Of E Coli Lipopolysaccharide O~ Nitrogen Excretion Fmentioning

confidence: 99%

Effects of Bacterial Endotoxins on Metabolism

Berry

Smythe

1961

The Journal of Experimental Medicine

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“…Typhoid endotoxin, after incubation in serum, failed to elicit antibodies when injected into rabbits (Skarnes, et al, 1958;Landy et al, 1959). Splitting of LPS during incubation with Cohn's fraction IV of serum was suggested by immunodiffusion patterns (Rudbach and Johnson, 1962).…”

Section: Antigenaemia and Severity Of Infectionmentioning

confidence: 99%

“…Taking into account the rapid antigenic alteration of lipopolysaccharides (LPS) after contact with plasma or plasma fractions (Skarnes et al, 1958;Landy et al, 1959;Rudbach and Johnson, 1962), we constructed sensitive immunoassays to detect monovalent (haptenic) and polyvalent 0-chain fragments of brucella LPS.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal study of brucellosis in mice by immunoassay of lipopolysaccharide-related antigens in blood and urine

Limet

Berbinschi

Cloeckaert

et al. 1988

Journal of Medical Microbiology

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Summary.Immunoassays based on latex agglutination or enzyme labelling (ELISA) were devised for the detection of lipopolysaccharide (LPS) of BrucelZa abortus, or its degradation products, in biological fluids of infected mice. The agglutination of latex was measured by counting of the remaining non-agglutinated particles in an automated immunoassay analyser. LPS was assayed by agglutination with antibodycoated latex and by competitive inhibition of agglutination of LPS-coated latex by anti-LPS antiserum. The inhibition system was more sensitive for the detection of degradation products of LPS. Correlation between ELISA and agglutination inhibition immunoassay was excellent (r = 0.96). Degradation of LPS occurred during storage, particularly when the samples contained specific antibodies. It could be prevented by removing cells immediately after collecting blood samples and by heating or alkaline denaturation of plasma.CBA/H mice were infected with various doses [65-(65 x lo6) cfu] of B. abortus biovar 3 cells and the course of infection followed by immunoassay of LPS-related antigens in serum and urine, and by titration of specific antibodies and non-specific circulating immune complexes. The concentration of LPS degradation products, assayed by the agglutination inhibition assay, was related to the severity of the infection, which was assessed by viable counts of B. abortus in the spleen. A close correlation was observed between the values of antigenaemia, the number of cfu (r = 0.97), and the inoculum size (r = 0.99 at day 28).

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“…The opposite was described by Farr and Lequire (32) who found an enhanced leucopenia (and fever) in normal rabbits when the pyrogen was injected in normal rabbit serum instead of in saline. Although inactivation of various properties of endotoxin by incubation in serum has been described by many workers (see Landy et al, (33)), the basis for refractoriness to leucopenia produced by normal serum, from a non-refractory donor, given some time before the vaccine is not easily understood.…”

Section: Tolerance To Pyrogenicit¥mentioning

confidence: 99%

Further Studies on Passive Transfer of Tolerance to Pyrogenicity of Bacterial Endotoxin

Freedman

1960

The Journal of Experimental Medicine

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In a previous report (1) we have described the passive transfer of tolerance to pyrogenicity of bacterial endotoxin. Such transfer was shown to depend upon the manner in which tolerance was induced in the donor animal, and this parameter has been further investigated. Both prolonged administration of the bacterial lipopolysaccharide, through 5 weeks, and daily injections of a large constant dose of endotoxin for a few days, permit demonstration of passive transfer, depending upon the magnitude of the test dose of the pyrogen in the recipient.Intravenously injected doses of endotoxin which cause a fever also elicit an almost immediate peripheral granulocytopenia. It has been thought that development of tolerance to the fever-producing effect of the toxin, which is accompanied by refractoriness to various other responses, extends to the acute leucopenia (2-5). If tolerance to leucopenia regularly paralleled tolerance to pyrogenicity the hypothesis suggesting endogenous leucocytic pyrogen as the mediator of endotoxin-induced fever (4) would be strengthened. Not finding refractoriness to the drop in peripheral white cell count in our rabbits passively tolerant to the pyrogenicity of endotoxin, we have studied the changes in numbers of circulating leucocytes in endotoxin-treated animals. We have not found tolerance to the leucopenia under conditions yielding substantial tolerance to pyrogenicity. A search of the literature largely supports this finding that tolerance to the pyrogenic effect becomes manifest without change in the acute leucopenic response (6)(7)(8)(9)(10)(11)(12).Following the demonstration by Grant and Whalen (13) of an endogenous pyrogen in the blood of rabbits injected with typhoid vaccine, an impressive series of experiments by Wood and coworkers (14-17) has led to the hypothesis that endotoxininduced fever is a consequence of the action of the exogenous pyrogen upon the leucocytes, or other cells, causing release of endogenous pyrogen which then acts upon the thermoregulatory centers of the brain (4). From an equally impressive series of researches, Bennett and associates (9,(18)(19)(20)(21)(22)(23)(24)(25) have shown that the fever seen after administration of endotoxin requires neither significant numbers of circulating leucocytes nor the presence of endogenous serum pyrogen, and have postulated a dual mechanism, involving a direct action of endotoxin, possibly accounting for the biphasic nature of the febrile response (3). 619on May 7, 2018 jem.rupress.org Downloaded from

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Inactivation of Endotoxin by a Humoral Component

Cited by 10 publications

References 13 publications

Effects of Bacterial Endotoxins on Metabolism

Effects of Bacterial Endotoxins on Metabolism

Longitudinal study of brucellosis in mice by immunoassay of lipopolysaccharide-related antigens in blood and urine

Further Studies on Passive Transfer of Tolerance to Pyrogenicity of Bacterial Endotoxin

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