Effects Of Bacterial Endotoxin Research Articles

Synergistic action of bacterial lipopolysaccharides on serum-stimulated DNA synthesis in mouse embryo fibroblasts.

It is widely recognized that agents which stimulate DNA synthesis and multiplication of animal cells in culture exert their activity through interaction with specific components of the cell surface. Examples include the lymphocyte mitogens Concanavalin A and phytohemagglutinin, insulin, and a class of growth-regulating protein hormones called somatomedins (1, 2). The biochemical nature of this interaction between growth-promoting substances and cell surfaces remains obscure. However, compounds which are known to cause alterations in cell membranes and which modulate the response of cells to specific mitogenic agents may prove to be useful tools with which to probe the complex mechanisms that regulate cell proliferation. Vaheri et al. (3) have previously reported that lipopolysaccharides (LPS) from gram-negative bacteria exert a dramatic mitogenic effect on stationary chicken embryo fibroblasts in culture. This effect was seen using extremely low concentrations of LPS (0.1-1 ng/ml). Although to our knowledge this has been the only report of such an effect of bacterial endotoxins on fibroblasts, LPS is widely recognized as a B cell specific mito-gen (4-7). In view of the above mentioned report (3), demonstrating a striking effect of LPS on the stimulation of DNA synthesis and growth of fibroblasts, it was of interest to further examine the multiplication-stimulating potential of LPS on another serum-dependent cell type, the mouse embryo fi-broblast. This report describes the effect of purified bacterial LPS on growth-related parameters of early passage mouse embryo fibroblasts. In contrast to the results reported previously by Vaheri et al. (3) on chicken cells, LPS has little or no effect by itself on cultured mouse cells. However, in the presence of calf serum, LPS exerts a potent synergistic effect on the stimulation of DNA synthesis in stationary confluent mouse fibroblasts.

Effect of BCG on hematopoietic stem cells: Experimental and clinical study

In (DBA/2×C57Bl/6) F1 mice the i.v. injection of 1 mg of living BCG does not increase the total number of CFU/s per femur, but a marked increase in the percentage of CFU/s in S phase is noted as early as the 8th hr. BCG injected i.v. also increases the absolute number of colony-forming units in agar per femur. The effect of BCG appears quite different from the known effect of bacterial endotoxin, and in particular it does not induce a significant increase in the level of CSF. The administration of BCG 24 hrs after treatment with a single dose of 200 mg/kg of cyclophosphamide significantly reduces the time of hematologic restoration, but the same dose of BCG given after a lethal dose of total body irradiation does not increase survival time in mice. These different effects of BCG seem to be related to the role of BCG in stimulating the multiplication maturation pool of the bone marrow without producing any increase in the reserve pool.

DNA synthesis in rat aortic endothelium: Effect of bacterial endotoxin and trauma

In an autoradiographic study the number of DNA-synthetizing aortic endothelial cells was compared at various intervals after an intravenous injection of bacterial endotoxin or saline in rats. In control animals approximately 0.5 per mill of endothelial cells were engaged in DNA synthesis, and only small variations were observed during the experiment. Bacterial endotoxin in doses of 5–500 μg produced a five- to ten fold increase in the number of labeled endothelial cells, reaching a maximum 48 h after the injection. Endotoxin also acted as a mitogen on mononuclear cells that infiltrated the strip of endothelial monolayer. Thorium dioxide and serotonin had no effect. Endotoxin did not stimulate DNA synthesis in endothelial cells of aortic segments incubated in vitro, but along the traumatized edges of the segments DNA-synthetizing endothelial cells were regularly found.

Efleet of Endotoxin on the Activity of Coagulation Factors VII, VIII and IX Produced during Organ Perfusion

SummaryThe effect of bacterial endotoxin on the production of factor VII, VIII and IX activities in isolated rabbit livers, spleens and kidneys was investigated. The organs were perfused for 4 hours with fluid devoid of coagulation activity and containing either endotoxin or glucose-saline diluent. A series of parallel experiments included an initial hour of perfusion to ensure removal of tissue-stored coagulation activity, and perfusion with platelet-rich plasma and protein synthesis inhibitors. Endotoxin increased factor VII production in all organs but especially in livers not subjected to the initial perfusion; this effect was abolished by actinomycin D and puromycin. Endotoxin had little effect on hepatic factor VIII and IX activities but it inhibited production of both factors in the kidney and of factor VIII in the spleen. Initial perfusion prevented this inhibition of splenic factor VIII activity. These data suggest that endotoxin increases factor VII synthesis and causes consumption of factors VIII and IX in perfused kidneys and, to a lesser extent, spleens. Also, initial perfusion appears to prevent the subsequent consumption of splenic factor VIII by endotoxin. This response may involve activation of some tissue-bound or stored factor(s) or may be due to removal of an inhibitor substance.

Immunologic and antineoplastic effects of endotoxin: role of membranes and mediation by cyclic adenosine-3',5'-monophosphate.

The fascination and difficulty of dealing with the biological effects of bacterial endotoxins (LPS) are largely due to the multitude of events that can be triggered in animals exposed to LPS; such a variety of possible effects of LPS reflects the unusually large number of target cells and cellular sites that can be affected directly or indirectly by these practically ubiquitous molecules. In our attempts to dissect and to understand these complex events, we can be aided significantly by developments in related areas that furnish clues about some aspects of LPS activity without elucidating all of the known parameters.

Selective effects of bacterial endotoxins on various subpopulations of lymphoreticular cells.

Evidence has been presented that the in-vitro mitogenic activity of bacterial endotoxins on lymphoreticular cells of mice is a property of the lipid A fraction and that this mitogenic activity affects approximately one-half of the spleen cells of murine strains studied. This mitogenic effect was shown to be thymus-independent and a property of a low-density cell subpopulation. These transformed cells have unique characteristics (including a highly developed endoplasmic reticulum) that distinguish them from cells transformed by thymus-dependent mitogens such as phytohemagglutinin. Evidence was reviewed that the initial mitogen-cell interaction involves both membrane binding and internalization and that mitogenic activity depends more on the nature and rate of the internalization process that results from binding than on the actual degree of binding. It is proposed that bacterial lipopolysaccharide (LPS) has a bifunctional nature, acting as both antigen and mitogen, and that this bifunctional nature makes LPS thymus-independent as an antigen. No evidence presently exists showing that the antigenand mitogen-responsive subpopulations are identical.

Vessel Wall and Thrombogenesis - Endotoxin

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.

The effects of bacterial endotoxin on the infection of mice with Trypanosoma cruzi.

SYNOPSISMice (Rockland strain) infected with Trypanosoma cruzi strain Tulahuén were treated with Escherichia coli endotoxin before, simultaneously with, and after inoculation of the parasites. The peak parasitemias of endotoxin‐treated mice were higher than those of nontreated infected animals, regardless of the time of endotoxin administration. Peak parasitemias occurred at the same time in infected nontreated mice as in animals given endotoxin before or simultaneously with the trypanosomes. If endotoxin was administered 24 hr after the infection, a delay in the peak parasitemia was noted. Changes in the survival time were not observed unless endotoxin was given 24 hr postinfection. Infected mice had an increasing susceptibility to the lethal effect of endotoxin. The LD50 of endotoxin decreased from 675 μg for normal mice to 230, 92, and 18 μg for infected animals 1, 3, and 8 days after the infection, respectively. In the infected mice, the endotoxin‐detoxifying ability of the spleen was found to be impaired.

Increased susceptibility of the kidney to ascending Escherichia coli infection following unilateral nephrectomy.

SUMMARY Renal infection and scarring following ascending Escherichia coli infection occurs more frequently in unilaterally nephrectomised rats than in sham nephrectomised animals. When ascending infection is established 7 weeks after unilateral nephrectomy at a time when compensatory growth of the remaining kidney is complete, no increase in the incidence of renal infection and scarring is noted. These observations show that growth due to compensatory hypertrophy sensitises the kidney to bacterial invasion and scarring. Ascending infection produces 2 separate effects on the hypertrophying kidney, namely impairment of growth and scar formation. Scar formation is associated with bacterial invasion of the renal parenchyma whereas impairment of growth may be due to an effect of bacterial endotoxin.

Antagonistic Effects of Bacterial Endotoxin and Phytohaemagglutinin upon the Primary Immune Response

Mice treated with one or several 1-mg doses of phytohaemagglutinin M (PHA-M) showed a suppressed immune response to human IgG. Similar suppression was obtained with 0.5 mg of phytohaemaggultinin P (PHA-P). Both, PHA-M and PHA-P, antagonized the adjuvant effect of <i>E. coli </i>endotoxin on the antibody response to human IgG. Maximal extent of antagonism between PHA-M or PHA-P, and endotoxin, depended on the relative time of administration of these biologically active substances.

Effects of Bacterial Endotoxin and Crowding on Pine Voles and White Mice

Effects of Bacterial Endotoxin and Crowding on Pine Voles and White Mice

Effects of bacterial endotoxin on hemopoietic colony-forming cells in the spleens of normal mice and mice of genotype S1-S1 d .

ABSTRACTMultiple doses of S. typhosa endotoxin caused an increase in the number of hemopoietic stem cells present in mouse marrow and spleen that could be detected using the spleen‐colony assay. This increase was inhibited by Colcemid, and by the genetically‐determined defect in hemopoiesis in mice of genotype S1/S1d. However, the defect in S1/S1d hosts did not prevent an endotoxin‐induced increase in the number of cells capable of forming colonies in cell culture. The results support the view that bacterial endotoxin acts, via a genetically‐controlled regulatory mechanism, to stimulate the proliferation of hemopoietic stem cells in the spleen.

Antibody formation in mice infected with Salmonella typhimurium by primary immunization with sheep erythrocytes or bacterial cells.

Infection of mice with a strain of Salmonella typhimurium, known to multiply in macrophages, resulted in a marked alteration of their antibody response to further antigenic stimulation with sheep red blood cells (sRBC) or killed bacterial cells. The mice infected with a wild-type S. typhimurium and simultaneously immunized with sRBC, showed a significantly stimulated immune response to sRBC as revealed by the increased number of hemolytic plaque-forming cells in their spleens during the period following such immunization. Whether the animals were infected intraperitoneally or intravenously did not affect the stimulant effect of the infection on the immune response to sRBC. Injection of killed bacteria in amounts up to 106 organisms, instead of infection with live organisms, did not elicit any effective enhancement of antibody formation to sRBC. In cases of attenuated S. typhimurium infection, the stimulant effect on antibody formation to sRBC was obvious in the mice infected with the organisms simultaneously with or 1 week prior to the sRBC injection, while a slight suppression of antibody formation was observed in mice infected 3 weeks before the injection with sRBC. A similar effect of the infection was observed when the serum anti-bacterial antibody response was examined after stimulation with bacterial antigens. The altered immune responses after Salmonella infection are discussed in relation to the adjuvant effect of bacterial endotoxins and also to the acquired immunity to mouse typhoid.

Effect of Bacterial Endotoxin on an Initial Infection of Nematospiroides dubius in Mice

Effect of Bacterial Endotoxin on an Initial Infection of Nematospiroides dubius in Mice

Effect of bacterial endotoxins on oxidative phosphorylation in the liver

Effect of bacterial endotoxins on oxidative phosphorylation in the liver

Inhibition of bone growth in vitro by endotoxin: histamine effect.

BECAUSE bacteria are found in close proximity to soft tissue and bone in the oral cavity, it seems logical that bacterial endotoxin could affect the metabolism of bone and contribute to the bone loss seen in periodontal disease. We investigated the effects of bacterial endotoxins on rapidly growing bone in an organ culture system. Also, because there is evidence that histamine affects the activity of endotoxin1–3, we cultured bones in an environment containing both endotoxin and histamine, and found that synthesis of structural protein was inhibited without affecting cell turnover.

Effects of bacterial endotoxin on operant behavior of the rat

Intraperitoneal administration of Escherichia coli endotoxin (19–625 μg/kg) depressed lever-pressing responses for food or water rewards in appropriately deprived rats. The responses for discriminated shock-avoidance were much less sensitive to the endotoxin. Single injection of the toxin induced marked tolerance to its behavioral effects.

Effect of bacterial endotoxin and inhibitors on tryptophan oxygenase induction in mouse liver slices.

Tryptophan oxygenase activity in mouse liver slices maintained in cluture medium, in Krebs-Ringer bicarbonate solution, or in homologous whole blood declined within 3 hr to about one-half the original level. Actinomycin D and puromycin accelerated the rate of decline, but endotoxin did not. Direct addition of tryptophan to the medium resulted in a higher than normal tryptophan oxygenase activity within 1 hr, and this was maintained well above that of control liver slices up to 6 hr. Triamcinolone, at a dose that doubles tryptophan oxygenase activity in vivo, had no effect on the enzyme in liver slices. Actinomycin and endotoxin did not alter the substrate induction of tryptophan oxygenase; however, puromycin did, but to a limited extent. Liver slices prepared from mice 4 hr after an injection of cortisone had a greater tryptophan oxygenase activity than those of controls. Either endotoxin or actinomycin D resulted in a more rapid decline of the enzyme when added to the slices than was observed in the controls.

Effect of Bacterial Endotoxin on Experimental Fungal Infections

Summary Escherichia coli endotoxin was administered to mice prior to challenge with 5 × 106 Candida albicans, 5 × 106 Rhizopus arrhizus or 1 × 106 Blastomyces dermatitidis organisms. When 100 or 400 µg endotoxin was given 1 hr prior to challenge with C. albicans, significant acceleration in mortality occurred, while the same doses of endotoxin given 24 hr before challenge delayed lethality. Similar protection but no enhancement of lethality was noted for R. arrhizus, while reproducible alterations in lethality were not demonstrable with B. dermatitidis. Protection against C. albicans appeared to have a bimodal character, being maximal at 24 hr and 6 days following endotoxin administration. Sterile sera were passively administered in amounts of 1.0 ml to normal mice, which were then challenged 1 hr later with C. albicans. Lethality was significantly delayed only in the animals receiving sera collected 24 hr after endotoxin but not in the groups receiving saline, normal sera or sera obtained 6 days following endotoxin. These studies demonstrate that serum factors are important in the initial phase of increased resistance against C. albicans induced by endotoxin.

The Effects of Bacterial Endotoxin on Rabbit Platelets

Summary The heat-labile plasma factor (HLPF) necessary for endotoxin-induced platelet injury in citrated plasma has been investigated. HLPF does not appear to be complement since no complement fixation occurs during the course of the platelet-endotoxin interaction. A functionally similar factor removed from plasma by zymosan appears to be the same in substitution experiments. The conditions employed in the zymosan adsorption also differentiate the adsorbed factor from complement. The relationship of this factor to properdin is discussed.