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PubMed1982

Immunochemical studies of lipopolysaccharide and partially degraded lipopolysaccharide from Bacteroides fragilis IPL E323.

A serologically heterogeneous lipopolysaccharide (LPS) was prepared from B. fragilis IPL E323 by phenol-water extraction and purification by ultracentrifugation. The LPS was split by hydrolysis with 1 per cent acetic acid into an acid-soluble polysaccharide and insoluble material. Gel filtration of the acid-soluble material on Bio-Gel P-60 gave a high-molecular-weight fraction eluted with the void volume (Vo), which was serologically heterogeneous, and low-molecular-weight materials eluted at 2.5 x Vo and 2.7 x Vo. Some material was also eluted at 2.9-3.0 x Vo. The oligosaccharides eluted at 2.5 x Vo and 2.7 x Vo showed an antibody-neutralizing capacity similar to that of the parent LPS. Galactose, glucose and rhamnose were the only sugars present in these fractions. The material eluted at 2.9-3.0 x Vo, which contained the same neutral sugars, but at another molar ratio, was serologically inactive. SImilar results were obtained when LPS from three other B. fragilis strains were treated in the same way.

Bacteroides fragilis↗
PubMed1998

Lipopolysaccharide from nonvirulent Ara+ Burkholderia pseudomallei isolates is immunologically indistinguishable from lipopolysaccharide from virulent Ara- clinical isolates.

Different lines of evidence suggest that a discrepancy between the distribution of Burkholderia (Pseudomonas) pseudomallei in the environment and the distribution of the disease melioidosis is attributable, at least in part, to phenotypic differences between clinical and some environmental isolates. Two antigenically and biochemically distinct biotypes have been described, only one of which is virulent. In this study, lipopolysaccharides (LPSs) were extracted by the proteinase K digestion method from a total of 214 B. pseudomallei isolates, and their immunoreactivities with sera from patients with different clinical spectra and with other infections were evaluated. With the exception of4 isolates from a total of 214 tested, the sodium dodecyl sulfate-polyacrylamide gel electrophoresis silver-staining profiles of the LPSs from the two biotypes showed identical ladder patterns that were typical for smooth LPSs from other gram-negative bacteria. The 210 isolates with typical LPS patterns (119 Ara- clinical, 13 Ara- soil, 70 Ara+ soil, and 8 reference National Type Culture Collection strains) also exhibited similar immunoblot profiles against pooled sera from patients with melioidosis and hyperimmune mouse sera. Concordant findings were noted in the indirect enzyme-linked immunosorbent assay with Ara- and Ara+ LPSs to coat the microtiter plates. The LPSs of the different B. pseudomallei biotypes appear antigenically indistinguishable. It is, therefore, unlikely that this component is related to the virulence and pathogenicity of B. pseudomallei.

Animals↗
PubMed1977

Inheritance of lipopolysaccharide-enhanced nonspecific resistance to infection and of susceptibility to endotoxic shock in lipopolysaccharide low-responder mice.

In a previous study, we demonstrated that lipopolysaccharide (LPS) and other bacterial immunostimulants, in contrast to their activity in a closely related high-responder subline, failed to elicit nonspecific resistance in LPS low-responder mice against Klebsiella pneumoniae infection. To investigate the type of inheritance controlling the LPS-induced nonspecific resistance to infection, the present study was performed in low- and high-responder C3H sublines and in F1 and F2 hybrids. In addition, F1 mice were backcrossed to each parental type. Inheritance of susceptibility to endotoxin was also tested in both sublines and their hybrids and backcross progeny. For these latter assays, mice were previously adrenalectomized because removal of this gland considerably enhances their sensitivity. Our present findings are consistent with the hypothesis that LPS enhances nonspecific resistance to infection and that susceptibility to endotoxin shock in the absence of corticoids may be determined by a single autosomal dominant gene.

Adrenalectomy↗
PubMed1977

Mitogenic response of mouse spleen cells and gelation of limulus lysate by lipopolysaccharide of Yersinia pestis and evidence for neutralization of lipopolysaccharide by polymyxin B.

Lipopolysaccharide (LPS) extracted with phenol and water from Yersinia pestis was compared with LPS of Escherichia coli for stimulation of deoxyribonucleic acid synthesis in mouse spleen cells (lymphocyte mitogenesis), gelation of limulus lysate, pyrogenicity in the rabbit, and susceptibility to inhibition of these activities by polymyxin B sulfate (PBS). LPS of Y. pestis stimulated deoxyribonucleic acid synthesis in mouse spleen cell cultures over the same quantitative range as LPS of E. coli. In the limulus tests and rabbit pyrogenicity studies, the LPS of Y. pestis was active but about 10 times less potent than E. coli LPS on a weight basis. PBS in concentrations from 1 to 10 microgram/ml diminished the rate of deoxyribonucleic acid synthesis in spleen cell cultures stimulated by LPS of both Y. pestis and E. coli. Addition of PBS to LPS of both Y. pestis and E. coli in a ratio of 100 parts of PBS to 1 part of LPS by weight increased by 10-fold the concentration of LPS required to produce gelation of limulus lysate and inhibited significantly pyrogenic responses in rabbits. These results demonstrating similarities of LPS of Y. pestis and E. coli may suggest that the pathogenesis of plague is similar to that of other gram-negative bacterial infections.

Endotoxins↗
PubMed1978

Inverse relationship between the susceptibility of lipopolysaccharide (lipid A)-pretreated mice to the hypothermic and lethal effect of lipopolysaccharide.

Mice pretreated (day 0) by a single injection of lipopolysaccharide (LPS) responded with hypothermic tolerance to (LPS) challenge on day 1 and with hypothermic hyperreactivity to LPS challenge on day 4. Reciprocally, mice pretreated similarly but with a higher challenge dose were hyperreactive with respect to LPS lethality on day 1, but highly tolerant to lethality when challenged on day 4. Hyperreactivity to LPS lethality (day 1) was evident from an accelerated onset of death as well as from a reduced 50% lethal dose in pretreated mice, the level of hyperreactivity being more pronounced with higher LPS pretreatment doses. Lethal hyperreactivity, however, was only seen after challenge with a 50% lethal dose of soluble LPS. In contrast, protection to lethality occurred after challenge with a 50% lethal dose of insoluble LPS (day 1). Tolerance to LPS lethality in mice was observed on day 4 after pretreatment with one (day 0) or four daily injections of LPS. Since reciprocal hyperreactivity (day 1) and cross-tolerance to lethality (day 4) could be achieved by treatment with Salmonella smooth- or rough-form LPS as well as with free lipid A, it was concluded that lipid A represents the active principle of LPS in inducing both hyperreactivity and tolerance to the lethal effect of LPS.

Animals↗
PubMed1978

Distribution of endotoxin (lipopolysaccharide) in the tissues of lipopolysaccharide-responsive and -unresponsive mice.

We examined the distribution of bacterial lipopolysaccharide (LPS) in LPS-responsive (C3H/St) and LPS-unresponsive (C3H/HeJ) mice. The results reported here demonstrate that the rates of removal of an immunological or a toxic dose of LPS from the circulation are the same in both strains of mice. C3H/St spleens accumulated significantly more LPS than C3H/HeJ spleens after the intravenous injection of either an immunogenic or a toxic dose of LPS. There was also a greater amount of LPS associated with cells teased from C3H/St spleens compared to those from C3H/HeJ spleens. After a toxic dose of LPS, there was more LPS in C3H/St lymph nodes, adrenals, lungs, kidneys, and heart than in the corresponding C3H/HeJ tissues. The accumulation of more LPS in tissues from C3H/St mice compared to C3H/HeJ mice suggests that these tissues are involved in the pathophysiological and, ultimately, the toxic effects of LPS. The differential accumulation of LPS in the tissues of these two strains may be the reason for the decreased responses of C3H/HeJ mice to LPS.

Animals↗
PubMed1979

Mechanism of lipopolysaccharide-induced tumor necrosis: requirement for lipopolysaccharide-sensitive lymphoreticular cells.

Lipopolysaccharide (LPS) induces rapid necrosis of intradermal fibrosarcomas in mice. The mechanism(s) by which LPS produces tumor necrosis has been investigated using histocompatible LPS-sensitive (C3H/HeN) and LPS-resistant (C3H/HeJ) mouse strains. C3H/HeN- or C3H/HeJ-derived fibrosarcomas were necrotized by LPS when they were grafted onto C3H/HeN mice but were not affected when growing on C3H/HeJ mice, indicating that LPS does not act directly on the tumor itself. In contrast, lethally X-irradiated C3H/HeJ mice exhibit necrosis of their tumors when reconstituted with C3H/HeN bone marrow cells, whereas C3H/HeN mice no longer exert LPS-induced tumor necrosis after the adoptive transfer of C3H/HeJ bone marrow cells. These findings clearly indicate that LPS produces necrosis of tumors by activating host lymphoreticular cells.

Animals↗
PubMed1979

Influence of lipopolysaccharide on graft versus host reactivity of lipopolysaccharide-unresponsive C3H/HeJ mice.

It was initially reported that lipopolysaccharide (LPS)-unresponsive C3H/HeJ mice are refractory to LPS at the B-lymphocyte level, but more recently it has been shown that other cells are similarly unaffected. The current study was undertaken to study an in vivo LPS-modulated disease process involving macrophage-T cell interactions. Adult CBA/J and C3H/HeJ mice were used as spleen donors, and graft versus host reactions were induced in BALB/c neonates. Prior LPS treatment of CBA/J adults decreased the ability of their spleen cells to cause fatal graft versus host disease in BALB/c neonates, whereas no difference was found between injection of spleen cells from normal or LPS-treated C3H/HeJ mice. Similar results were obtained with these cell types when the mouse spleen mixed leukocyte culture system was used. In a carbon clearance assay for stimulation of the reticuloendothelial system with LPS, it was found that the rate of phagocytosis was significantly increased in BALB/c and CBA/J mice 72 h after inoculation of LPS. No stimulation was seen in rate of carbon uptake in the C3H/HeJ animals after treatment with phenol-extracted LPS or with butanol-extracted LPS. An LPS-induced protective serum factor was produced only in the LPS-responsive CBA/J mice and was specific for the syngeneic cells.

Animals↗
PubMed1983

Use of mice tolerant to lipopolysaccharide to demonstrate requirement of cooperation between macrophages and lymphocytes to generate lipopolysaccharide-induced colony-stimulating factor in vivo.

Injection of lipopolysaccharide (LPS) into mice was followed by a rapid elevation of colony-stimulating factor (CSF) in the serum. A second, challenging injection of LPS given 3 to 4 days later failed to induce elevated levels of CSF in the serum. Such mice tolerant to LPS were used as an experimental tool to identify the CSF-producing cells which respond to LPS. We observed that generation of LPS-induced CSF in mice tolerant to LPS could be restored by an intraperitoneal injection of spleen cells 24 h before the challenging injection of LPS. Depletion of the adherent cells from the spleen cells reduced the ability of the splenic lymphocytes to restore the capacity of the mice tolerant to LPS to generate serum CSF. Reconstitution of the splenic lymphocytes with 5% thioglycolate-elicited peritoneal macrophages, however, reestablished the restorative capacity of these cells, whereas almost no restoration was observed after direct injection of elicited peritoneal macrophages. These data suggest that the spleen cells are active in generating CSF, provided that macrophages are present and can interact with the splenic lymphocytes to generate LPS-induced CSF in the serum.

Animals↗
PubMed1983

Common lipopolysaccharide specificity: new type of antigen residing in the inner core region of S- and R-form lipopolysaccharides from different families of gram-negative bacteria.

A new antigenic specificity, referred to here as common lipopolysaccharide (LPS) specificity, is described in the LPSs of gram-negative bacteria belonging to various families. The specificity is present in S- and R-form LPS but absent in Re mutants of different enterobacterial genera. By the use of purified LPS and monospecific antibodies obtained by immunoabsorption, the specificity is differentiated from the known core specificities of the genus Salmonella and the lipid A specificity by aid of the passive hemolysis and passive hemolysis inhibition test. In Salmonella minnesota R-form LPS, the specificity may be cryptic (R345, Rb2 mutant) or partly exposed in the intact molecule (R7, Rd1 mutant). The specificity is either demasked or completely exposed after mild acid hydrolysis for a short time, whereas it is destroyed after prolonged hydrolysis. Periodate oxidation, reduction, and hydrolysis under conditions that do not affect the ketosidic linkages of 2-keto-3-deoxyoctulosonic acid destroy the specificity in R4 (Rd2 mutant) LPS, but do not do so in R7 LPS. It is suggested that 2-keto-3-deoxyoctulosonic acid and a following neutral sugar are the compositional requirements for expressing the specificity.

Bacteroidaceae↗
PubMed1984

Analyses of gonococcal lipopolysaccharide in whole-cell lysates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis: stable association of lipopolysaccharide with the major outer membrane protein (protein I) of Neisseria gonorrhoeae.

The lipopolysaccharide (LPS) of Neisseria gonorrhoeae whole-cell lysates and proteinase K-digested lysates was examined and compared with purified homologous LPS by a method which preferentially stains LPS in polyacrylamide gels. The silver-stained profile of gonococcal LPS in the proteinase K-digested lysate was similar to that of homologous purified LPS; however, the LPS profile in whole-cell lysates was much smaller than that of digested lysates or purified LPS. Conditions of solubilization did not affect these differences. Since it is known that LPS migrates in a unique fashion in second-dimension electrophoresis, the location of LPS in the whole-cell lysates was probed by second-dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a variety of stains and radiolabels. Results from these experiments indicated a stable and reproducible association of LPS with proteins ranging between 23,000 to 36,000 in Mr, in particular major outer membrane protein I. In addition to staining with the silver method, which preferentially stains LPS, the putative LPS was resistant to digestion by proteinase K, did not stain with Coomassie brilliant blue, and was not labeled extrinsically with 125I (Iodogen method) or intrinsically with [35S]methionine. Analysis of two-dimensional gels by immunoblotting with rabbit antisera prepared from protein I bands removed from a polyacrylamide gel revealed the presence of antigens in the same area of the gel (below proteins that were 23,000 to 36,000 in Mr). Antibodies to constituents which migrated below the diagonal were essentially removed by adsorption of antisera with purified LPS, as were antibodies to homologous LPS and LPS in proteinase K-digested whole-cell lysates. Immunoblotting with a monoclonal antibody specific for LPS demonstrated reactivity of the antibody with LPS and with the protein I band. On the basis of these data, we conclude that protein I and perhaps other proteins in the whole-cell lysate are stably associated with LPS; this complex is resistant to dissociation in sodium dodecyl sulfate at high temperature (approximately 100 degrees C) but does, for unknown reasons, dissociate with electrophoresis in the second dimension. The association of LPS with protein antigens in sodium dodecyl sulfate-polyacrylamide gels adds another dimension of complexity to analysis of these antigens by immunoelectroblotting. Furthermore, the tight association of LPS with the major outer membrane protein I may alter the nature of the immune response generated by "purified" protein I vaccine antigens. The possible role of protein-LPS complexes in the pathogenesis of gonorrhea is discussed.

Bacterial Outer Membrane Proteins↗
PubMed1985

Coprecipitation of lipopolysaccharide and the 39,000-molecular-weight major outer membrane protein of Haemophilus influenzae type b by lipopolysaccharide-directed monoclonal antibody.

The major outer membrane protein of Haemophilus influenzae type b (Hib) with an apparent molecular weight of 39,000 (39K) was purified from three different Hib strains and was shown to be free from detectable contamination with other proteins. However, these purified 39K protein preparations were found to contain Hib lipopolysaccharide (LPS). Immunization of rats with these 39K protein preparations resulted in the production of antisera containing both 39K protein-directed and LPS-directed antibodies, as determined by Western blot analysis. The reactivity pattern of the LPS-directed serum antibodies with different Hib strains was identical to the reactivity of these Hib strains with a set of monoclonal antibodies (mabs) previously shown to immunoprecipitate the 39K protein in a radioimmunoprecipitation (RIP) system. Examination of the antigenic specificities of the 39K protein-immunoprecipitating mabs by using Western blot analysis showed that these mabs were actually directed against Hib LPS. RIP analysis of 125I-labeled Hib cells and 32P-labeled Hib cells revealed that the 39K protein and LPS existed as a complex in a RIP system, which resulted in the coprecipitation of both antigens by LPS-directed mabs. The interaction between LPS and the 39K protein was highly selective for this protein and did not involve other outer membrane proteins. The LPS/39K protein complex could be reconstituted by mixing purified LPS and purified 39K protein; it could also be reconstituted with 39K protein from one Hib strain and LPS from another Hib strain. These findings have necessitated the reinterpretation of previous studies involving the 39K protein-immunoprecipitating mabs. Of primary importance is the fact that the demonstrated immunoprotective ability of a 39K protein-immunoprecipitating mab (E. J. Hansen, S. M. Robertson, P. A. Gulig, C. F. Frisch, and E. J. Haanes, Lancet i:366-368, 1982) must now be regarded as evidence that antibody directed against Hib LPS can be protective against experimental Hib disease.

Animals↗
PubMed1991

Differential effects of monophosphoryl lipid A on expression of suppressor T cell activity in lipopolysaccharide-responsive and lipopolysaccharide-defective strains of C3H mice.

Lipopolysaccharide (LPS)-responsive and LPS-defective strains of C3H mice did not differ in the capacity to make an antibody response to type III pneumococcal polysaccharide or in the degree of thymus-derived suppressor cell (Ts) activity generated following exposure to type III pneumococcal polysaccharide. However, treatment with monophosphoryl lipid A (MPL) abolished the expression of Ts function in LPS-responsive but not LPS-defective mice. Since this effect was elicited by different preparations of MPL, it appears to be a general property of MPL mediated by direct action of MPL on activated Ts.

Animals↗
PubMed1993

Chemical properties of lipopolysaccharides from spotted fever group rickettsiae and their common antigenicity with lipopolysaccharides from Proteus species.

The lipopolysaccharides (LPS) isolated from spotted fever group (SFG) rickettsia strains Thai tick typhus TT-118 and Katayama were characterized by chemical analyses, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay (ELISA), and immunoblotting. These LPS did not contain heptose, but they contained 3-deoxy-D-manno-octulosonic acid (KDO), glucosamine, quinovosamine, phosphate, ribose, an unknown neutral sugar, and palmitic acid. Resolution of the apparent molecular masses of these LPS by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and staining with silver showed ladder-like bands. In an ELISA, convalescent-phase sera from 10 patients with Japanese spotted fever reacted with LPS from the Katayama strain, and 90% (9 of 10) of these sera also reacted with LPS isolated from Proteus vulgaris OX2. Immunoblotting revealed that the sera reacted with the high-molecular-mass bands of LPS from SFG rickettsiae, in addition to those of OX2 LPS. In an ELISA, immunoglobulin M antibodies from these sera reacted with the O-polysaccharide and lipid A portions of LPS from P. vulgaris OX2. The epitopes common to LPS of SFG rickettsiae and P. vulgaris OX2 may be in the O-polysaccharide and lipid A portions.

Antibodies, Bacterial↗
PubMed1998

Structural properties of lipopolysaccharides from Rickettsia typhi and Rickettsia prowazekii and their chemical similarity to the lipopolysaccharide from Proteus vulgaris OX19 used in the Weil-Felix test.

The lipopolysaccharides (LPSs) isolated from typhus group (TG) rickettsiae Rickettsia typhi and Rickettsia prowazekii were characterized by chemical analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by silver staining. LPSs from two species of TG rickettsiae contained glucose, 3-deoxy-D-manno-octulosonic acid, glucosamine, quinovosamine, phosphate, and fatty acids (beta-hydroxylmyristic acid and heneicosanoic acid) but not heptose. The O-polysaccharides of these LPSs were composed of glucose, glucosamine, quinovosamine, and phosphorylated hexosamine. Resolution of these LPSs by their apparent molecular masses by SDS-PAGE showed that they have a common ladder-like pattern. Based on the results of chemical composition and SDS-PAGE pattern, we suggest that these LPSs act as group-specific antigens. Furthermore, glucosamine, quinovosamine, and phosphorylated hexosamine were also found in the O-polysaccharide of the LPS from Proteus vulgaris OX19 used in the Weil-Felix test, suggesting that they may represent the antigens common to LPSs from TG rickettsiae and P. vulgaris OX19.

Antigens, Bacterial↗
PubMed1998

Lipopolysaccharide-related stimuli induce expression of the secretory leukocyte protease inhibitor, a macrophage-derived lipopolysaccharide inhibitor.

Mouse secretory leukocyte protease inhibitor (SLPI) was recently characterized as a lipopolysaccharide (LPS)-induced product of macrophages that antagonizes their LPS-induced activation of NF-kappaB and production of NO and tumor necrosis factor (TNF) (F. Y. Jin, C. Nathan, D. Radzioch, and A. Ding, Cell 88:417-426, 1997). To better understand the role of SLPI in innate immune and inflammatory responses, we examined the kinetics of SLPI expression in response to LPS, LPS-induced cytokines, and LPS-mimetic compounds. SLPI mRNA was detectable in macrophages by Northern blot analysis within 30 min of exposure to LPS but levels peaked only at 24 to 36 h and remained elevated at 72 h. Despite the slowly mounting and prolonged response, early expression of SLPI mRNA was cycloheximide resistant. Two LPS-induced proteins-interleukin-10 (IL-10) and IL-6-also induced SLPI, while TNF and IL-1beta did not. The slow attainment of maximal induction of SLPI by LPS in vitro was mimicked by infection with Pseudomonas aeruginosa in vivo, where SLPI expression in the lung peaked at 3 days. Two LPS-mimetic molecules-taxol from yew bark and lipoteichoic acid (LTA) from gram-positive bacterial cell walls-also induced SLPI. Transfection of macrophages with SLPI inhibited their LTA-induced NO production. An anti-inflammatory role for macrophage-derived SLPI seems likely based on SLPI's slowly mounting production in response to constituents of gram-negative and gram-positive bacteria, its induction both as a direct response to LPS and as a response to anti-inflammatory cytokines induced by LPS, and its ability to suppress the production of proinflammatory products by macrophages stimulated with constituents of both gram-positive and gram-negative bacteria.

Animals↗
PubMed1998

Human antibody response to Helicobacter pylori lipopolysaccharide: presence of an immunodominant epitope in the polysaccharide chain of lipopolysaccharide.

We have examined the antibody response to Helicobacter pylori lipopolysaccharides (LPS) in humans. We used sera from patients with gastroduodenal diseases and healthy adults infected or not infected with H. pylori. Data from the experiments for antibody binding to LPS suggested that the polysaccharide chains from many H. pylori strains showed high immunogenicity in humans. Sera from most (above 70%) H. pylori-infected individuals contained immunoglobulin G (IgG) antibodies against the polysaccharide region highly immunogenic H. pylori LPS. The IgG titers of individual serum samples that reacted strongly with highly immunogenic LPS were quite similar (r2 = 0.84 to 0.98). The results suggest wide distribution among H. pylori strains of a highly antigenic epitope in the polysaccharide moieties of their LPS. Also, the similarity in the titers of individual serum samples against highly immunogenic LPS points to the existence of epitopes sharing a common structural motif. However, some strains showed low antigenicity, even those with polysaccharide-carrying LPS. The dominant subclass of IgG that reacted with the highly immunogenic LPS was IgG2, which was preferentially raised against polysaccharide antigens. Recently, a structure that mimics that of the Lewis antigens was identified in the O-polysaccharide fraction of H. pylori LPS; however, no correlation between antigenicity of the polysaccharide chain in humans and the presence of Lewis antigens was found. The IgA and IgM titers against H. pylori LPS seemed to be mostly nonspecific and directed against lipid A. In a few cases, however, sera from individuals infected with H. pylori gave strong IgA and IgM titers against the highly immunogenic polysaccharide. In conclusion, the LPS of many H. pylori strains possess an antigenic epitope in their polysaccharide regions that is immunogenic in humans. However, our results show that the antigenic epitope is unlikely to be immunologically related to structures mimicking Lewis antigens.

Adult↗
PubMed2003

Porphyromonas gingivalis lipopolysaccharide antagonizes Escherichia coli lipopolysaccharide at toll-like receptor 4 in human endothelial cells.

E. coli lipopolysaccharide (LPS) induces cytokine and adhesion molecule expression via the toll-like receptor 4 (TLR4) signaling complex in human endothelial cells. In the present study, we investigated the mechanism by which Porphyromonas gingivalis LPS antagonizes E. coli LPS-dependent activation of human endothelial cells. P. gingivalis LPS at 1 micro g/ml inhibited both E. coli LPS (10 ng/ml) and Mycobacterium tuberculosis heat shock protein (HSP) 60.1 (10 micro g/ml) stimulation of E-selectin mRNA expression in human umbilical vein endothelial cells (HUVEC) without inhibiting interleukin-1 beta (IL-1beta) stimulation. P. gingivalis LPS (1 micro g/ml) also blocked both E. coli LPS-dependent and M. tuberculosis HSP60.1-dependent but not IL-1beta-dependent activation of NF-kappaB in human microvascular endothelial (HMEC-1) cells, consistent with antagonism occurring upstream from the TLR/IL-1 receptor adaptor protein, MyD88. Surprisingly, P. gingivalis LPS weakly but significantly activated NF-kappaB in HMEC-1 cells in the absence of E. coli LPS, and the P. gingivalis LPS-dependent agonism was blocked by transient expression of a dominant negative murine TLR4. Pretreatment of HUVECs with P. gingivalis LPS did not influence the ability of E. coli LPS to stimulate E-selectin mRNA expression. Taken together, these data provide the first evidence that P. gingivalis LPS-dependent antagonism of E. coli LPS in human endothelial cells likely involves the ability of P. gingivalis LPS to directly compete with E. coli LPS at the TLR4 signaling complex.

Antibiosis↗