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C Galanos

Publications and source records attributed to C Galanos.

189 records · Page 11Linked to original sources
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Culture and biological activity of Propionibacterium acnes.

Administration of killed Propionibacterium acnes to experimental animals leads to the development of hypersensitivity to the lethal and cytokine-inducing effects of endotoxin. This sensitizing property of P. acnes is not always expressed by different bacterial preparations. Its expression depends very much on the conditions employed for the cultivation of this microorganism. The present study investigates which culturing conditions result in P. acnes preparations with optimal sensitizing properties. The composition of the medium, the culturing time and temperature as well as the type of cultivation (in minifermentor or stationary culture) were all varied for this purpose. The resulting bacterial preparations were killed at 65 degrees C for 1 h and tested for sensitizing activity. The results show that stationary cultures of P. acnes grown at 37 degrees C for 4 to 5 days in the appropriate medium produce biologically active preparations with satisfactory sensitizing activity.

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Role of lipopolysaccharide susceptibility in the innate immune response to Salmonella typhimurium infection: LPS, a primary target for recognition of Gram-negative bacteria.

Lipopolysaccharide is an important recognition marker by virtue of which the innate immune system senses and reacts against Gram-negative bacteria invading the LPS susceptible host. This review deals with the factors affecting LPS susceptibility and with the role of the latter in the course and outcome of Salmonella typhimurium infection.

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Lipopolysaccharides: structural principles and biologic activities.

Structural principles of the three regions of the lipopolysaccharide molecule are briefly discussed. One of the recently available, chemically synthesized lipid A analogues has been tested for biologic activities. The preparation was found to be toxic, pyrogenic, and mitogenic. The amounts, however, needed for expression of effects similar to those of lipid A were about 500 times higher. These investigations are aimed at verifying the proposed structure of lipid A and at evaluating structure-activity relationships.

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The fate of lipopolysaccharide in rats: evidence for chemical alteration in the molecule.

The fate of smooth form lipopolysaccharide (LPS) from Salmonella abortus-equi injected intravenously in rats was studied. In the circulation, the LPS formed a stabile complex with high density plasma lipoprotein and was cleared from the blood primarily into the liver at a slow rate (over a period of two days). In the liver, LPS was first detectable in Kupffer's cells and granulocytes; from there it was later redistributed (after two days) into hepatocytes. While it was in the circulation, no evidence for alteration in the chemical structure of the LPS was found. However, partial loss of fatty acids occurred in the liver and also other organs such as the spleen. The excretion of chemically altered LPS continued for several weeks, mainly via the feces and, to a small extent, in the urine.

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Immunogenic properties of lipid A.

Lipid A, the endotoxic principle of gram-negative bacterial lipopolysaccharides, when suitably exposed on the surface of bacterial cells, becomes immunogenic, eliciting the formation of antibodies specific to lipid A. Antibodies to lipid A occur naturally in the serum of normal humans and many animal species; the two exceptions found so far are mice (all strains tested) and guinea pigs. Antibodies to lipid A occur more frequently in patients with infections caused by gram-negative bacteria, such as urinary tract infections. Antibodies to lipid A interacted with free lipid A but not with lipid A as present in the intact lipopolysaccharide molecule. Antibodies to lipid A were induced in rabbits, but not in mice, following a single injection of immunogenic lipid A. Because of similarities between the lipid A of many gram-negative bacteria, antibodies to lipid A showed wide cross-reactions. With regard to biologic activity, antibodies to lipid A have been variously shown to be protective, damaging, or without effect.

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Lipopolysaccharide-induced elaboration of interleukin 1 by human monocytes: use for detection of lipopolysaccharide in serum and the influence of serum-lipopolysaccharide interactions.

An assay of interleukin 1 (IL-1) production by human monocytes was used to detect minute amounts of bacterial lipopolysaccharide (LPS) in sera or serum components designed for use in experiments or for injection into humans. Elaboration of IL-1 is a more sensitive criterion for the presence of LPS than is the rabbit pyrogenicity assay, and contamination of a given solution with LPS can be semiquantitatively determined by comparison with a standard. Interaction of (exogenously added) LPS with serum interferes with the recognition of LPS by monocytes but in a manner different from that encountered in the limulus test. Recognition of LPS by monocytes was not affected by the presence of naturally occurring antibodies to LPS. With use of IL-1 elaboration as an indicator, the presence of functionally active LPS in the sera of some patients with sepsis could be demonstrated.

Adult↗
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Endotoxin tolerance: regulation of cytokine production and cellular changes in response to endotoxin application in cancer patients.

Endotoxin (lipopolysaccharide, LPS) has the property of inducing tolerance to its own biological effects. This phenomenon has been extensively studied in animal models but only few studies exist on the regulation in humans. Here we describe experiments designed to determine the cytokine regulation and cellular changes in humans during induction of LPS tolerance after repeated LPS injections. Intravenous administration of purified LPS Salmonella abortus equi to cancer patients induces high amounts of circulating tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF). Repeated injections of LPS at daily intervals resulted in a marked downregulation of the cytokine response and in the case of TNF-alpha, IL-8, G-CSF, and M-CSF the cytokine response was reduced to baseline levels. In contrast, significant increases in serum IL-6 were detected up to day 5 of repeated LPS injections. Hematological changes included transient decreases in WBCs affecting granulocytes, monocytes, and lymphocytes, followed by a marked granulocytosis. The drop in WBCs remained unaltered throughout the 5 day course of repeated LPS injections whereas the granulocyte overshoot recovery diminished gradually. When PBMCs of the cancer patients were restimulated ex vivo a marked enhancement of the capacity to produce TNF-alpha, IL-113, and IL-6 occurred, which is in contrast to the decreasing TNF-alpha serum levels obtained in vivo. In parallel, a shift in monocyte subpopulations from CD14+/CD16- to CD14+/CD16+ cells was observed. The data provide evidence that different mechanisms are implicated in the cytokine downregulation following repeated LPS injections to cancer patients. Furthermore, PBMCs from LPS tolerant patients do not demonstrate a reduction in their capacity to produce cytokines.

Antigens, CD↗
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Antitumoral effects of lipopolysaccharides, tumor necrosis factor, interferon and activated macrophages: synergism and tissue distribution.

Treatment of C57BL/6 mice bearing Lewis lung carcinoma or of BALB/c mice bearing EMT6 sarcoma with tumor necrosis factor (TNF), lipopolysaccharides (LPS) or interferon caused necrosis of the solid tumors and regression. Toxicity was observed in tumor-bearing animals when TNF or LPS were used at effective antitumoral doses. Similar antitumoral effects could be achieved using less than 1 million macrophages from C57BL/6, lung of from BALB/c peritoneal cavity expanded in vitro, and spontaneously fully activated to cytotoxicity during culture. This effect, observed after transfer twice a week by intravenous or peritumoral route, was not dependent on histocompatibility. Additive effects were observed after combined treatment with activated macrophages and a low dose of LPS or TNF. The biodistribution of labelled LPS and of labelled cytotoxic macrophages was studied in tumor-bearing mice. Although, as expected, LPS was concentrated essentially in the liver, a slow accumulation in the center of the tumor was observed. Macrophages injected intravenously accumulated in the lung and were then redistributed towards liver, kidney and the tumor periphery. Macrophages injected locally remained essentially in the tumor periphery with a slow redistribution in the body. The complementary localization of LPS and of cytotoxic macrophages respectively in the center and periphery of solid tumors might explain their synergism.

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