Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell walls of gram-negative bacteria contain several biologically active components, including lipopolysaccharide (LPS), lipoprotein, and protein 1. The effects of these individual components and a synthetic analog of lipoprotein, TPP, on several activation parameters of glomerular mesangial cells (MC) were examined. Prostaglandin secretion, synthesis of the autogrowth factor, mesangial interleukin-1 (IL-1), and new synthesis of cellular proteins were assessed as markers of MC activation. All bacterial cell wall components evaluated were active in varying degrees as stimulants of prostaglandin secretion. In general, PGE was the predominant product. TPP and protein 1 also induced substantial secretion of thromboxane. Each cell-wall component was effective in stimulating mesangial IL-1 secretion. The activation of MC was associated with the enhanced synthesis of many cellular proteins in addition to IL-1. Stimulation by these bacterial components was dependent on the state of the mesangial cell cycle, because nonproliferating cells did not respond to these factors. Activation of MC by gram-negative bacterial cell wall components, with release of vasoactive prostaglandins and peptide mitogens, may be responsible for some of the glomerular hemodynamic alterations and cellular proliferative events associated with sepsis or chronic bacterial infection.
 ...
PMID:Activation of glomerular mesangial cells by gram-negative bacterial cell wall components. 305 3

The Shwartzman reaction is a classic biologic response in which the coagulation system is activated in vivo. Cellular initiation of the extrinsic coagulation protease cascade can be mediated by one or more limbs of the lymphoid response to diverse biological stimuli. The T cell-instructed monocyte and macrophage responses that have been implicated are mediated by a number of different cellular pathways and are elicited not only by antigens and allogeneic cells but also by other stimuli such as immune complexes and the lipid A moiety of bacterial lipopolysaccharide (LPS). The latter response has been implicated in the pathogenesis of the disseminated intravascular coagulation associated with bacterial infection. In the rapid collaborative cellular pathway response to LPS, we have described a relatively rigorous requirement for T helper cells in induction of the biosynthesis of tissue factor and Factor VII by monocytes. To elucidate potential regulatory aspects of this cellular procoagulant response, we provide the first evidence for the existence of T suppressor cells for the cellular procoagulant response to LPS by the rapid T cell-instructed pathway. Human peripheral blood lymphocytes were separated by cytoaffinity into Fc gamma-positive and Fc mu-positive cells and were characterized for their functional properties in the procoagulant response. T mu cells mediated the monocyte response, consistent with their identity with instructor cells. T gamma cells suppressed the response of monocytes to LPS in the presence of T mu cells, suggesting that they possess suppressor function for this response. The T gamma suppressor cells required stimulation by LPS to express their suppressor function and they exerted their suppressive effect directly on the monocyte. The existence and participation of LPS-responsive T suppressor cells on the cellular procoagulant response in vitro add a new dimension to the complexity of the rapid pathway of the collaborative cellular procoagulant response and may be important in the pathogenesis of disseminated intravascular coagulation.
 ...
PMID:Regulatory roles of T mu and T gamma cells in the collaborative cellular initiation of the extrinsic coagulation pathway by bacterial lipopolysaccharide. 316 8

ICR mice were infected intravesically with a virulent (7343) or a nonvirulent (U+) Escherichia coli strain. The U+ strain induced considerably more shedding of uroepithelial cells than did the 7343 strain. The stimulus for this shedding was shown to be associated with lipopolysaccharide and was abrogated by pretreatment with aprotinin. Desquamation commenced within 1 h postinjection, and the cells that were shed proved to be viable. Comparison of C3H/HeJ and C3H mice revealed that only the latter responded to shedding inducers. However, C3H/HeJ mice succumbed to a systemic infection on injection of 10(6) U+ cells intravesically, whereas other mouse strains required a 100-fold dose of bacteria for this effect. Since the first stage of a bacterial infection entails adherence of the microbes to epithelial cells, inducible shedding is an antimicrobial defense mechanism.
 ...
PMID:Endotoxin-induced shedding of viable uroepithelial cells is an antimicrobial defense mechanism. 328 2

We have produced monoclonal antibodies (MoAb) to the Rb core and lipid A regions of Salmonella lipopolysaccharide (LPS) and have assessed their ability to inhibit LPS-mediated mitogenic responses in vitro, and to protect against LPS toxicity and lethal Salmonella infection in vivo. Monoclonal antibodies RC-8 and RC-16 were specific for LPS Rb core determinants, and MoAb LA-1, LA-2, LA-3, LA-4 and LA-5 were specific for lipid A. Anti-lipid A MoAb LA-2, LA-3 and LA-5 were found to abrogate mitogenic responses of C3H/HeN spleen cells to smooth S. typhimurium LPS (S LPS) and to rough S. minnesota R595 LPS (Re LPS). Monoclonal antibody LA-5 was effective in extending the median length of survival of C3H/HeN mice challenged with a lethal dose of either S LPS or Re LPS. Antibody LA-2 could extend the median length of survival of C3H/HeJ mice challenged with Re LPS but not with S LPS, and failed to extend significantly the length of survival of S LPS-challenged C3H/HeN and DBA/2 mice. Neither 20 micrograms of anti-Rb core or anti-lipid A MoAb nor 200 micrograms of anti-lipid A MoAb were able to protect C3H/HeN or BALB/c mice, respectively, against lethal infection with S. typhimurium SR-11. These results suggest that the importance of anti-lipid A antibodies in host defence may lie more in their ability to neutralize pathological effects of LPS, than in their ability to protect against bacterial infection.
 ...
PMID:Monoclonal antibodies to salmonella lipopolysaccharide: functional analysis of anti-lipid A antibodies. 329 50

Administration in vivo of recombinant interleukin 2 (rIL-2) to mice induces a polyclonal IgM response. When co-administered with a specific antigen, rIL-2 can enhance concentrations of murine IgM antibodies specific for the antigen by fivefold within 7 d of initial treatment. IgM antibodies that are induced after injection of rIL-2 include antibodies specific for J5, a cell wall core lipopolysaccharide (LPS) antigen that is shared by the different members of the Enterobactericeae family. We report here that mice pretreated with rIL-2 or immunized with J5 antigen 7 d before bacterial challenge were protected from septic death that is caused by intraperitoneal challenges with Escherichia coli. Optimal protection was provided by a combined J5 antigen and rIL-2 treatment. Acquisition of the rIL-2 and J5 antigen-induced protection against lethal bacterial infection coincided temporally with maximal serum IgM titers that also contained IgM antibodies specific for the J5 antigen. In passive immunization experiments, the affinity-purified IgM fraction in sera of rIL-2-treated animals was identified as necessary and sufficient for protection. The IgM-depleted serum had no protective effect. The nonspecific augmentation of host-defense mechanisms without the induction of endotoxin manifestations makes rIL-2 a potential candidate to any alternative LPS-containing vaccines for the prevention of bacterial infections by gram-negative organisms since the core LPS antigen is shared among gram-negative bacteria.
 ...
PMID:Administration in vivo of recombinant interleukin 2 protects mice against septic death. 329 1

Bacterial infection of the mammalian bloodstream can lead to overwhelming sepsis, a potentially fatal syndrome of irreversible cardiovascular collapse (shock) and critical organ failure. Cachectin, also known as tumour necrosis factor, is a macrophage-derived peptide hormone released in response to bacterial lipopolysaccharide, and it has been implicated as a principal mediator of endotoxic shock, although its function in bacterial sepsis is not known. Anaesthetized baboons were passively immunized against endogenous cachectin and subsequently infused with an LD100 dose of live Escherichia coli. Control animals (not immunized against cachectin) developed hypotension followed by lethal renal and pulmonary failure. Neutralizing monoclonal anti-cachectin antibody fragments (F(ab')2) administered to baboons only one hour before bacterial challenge protected against shock, but did not prevent critical organ failure. Complete protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion. These results indicate that cachectin is a mediator of fatal bacteraemic shock, and suggest that antibodies against cachectin offer a potential therapy of life-threatening infection.
 ...
PMID:Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. 331 66

Muramyl dipeptide is the smallest biologically active fragment of the lipopolysaccharide (LPS) moiety of gram-negative bacteria cell walls. The present report demonstrates that this product, associated with the immune response to bacterial infection, can modify CNS activity. Specifically, it is demonstrated that 6-0-stearoyl-muramyl dipeptide (MDP) can attenuate opiate withdrawal severity in a dose-dependent fashion when injected directly into areas of the brain essential for this phenomenon. In addition, MDP alters both baseline and postnarcotic electrophysiologic responses of four brain areas essential for various opioid activities. Similar findings have been reported for interferon-alpha (IFN-alpha), a peptide associated with the immune response to virus. Yet, even though MDP and IFN are shown to exert similar effects on opioid activity, there are also some very distinct differences in the actions of both of these immune response products. These observations suggest that central opioid systems may provide targets for the perception as well as the differentiation of afferent immunologic sensory input to the brain.
 ...
PMID:Neuroimmune intercommunication, central opioids, and the immune response to bacterial endotoxin. 334 5

The effects of intra-articular injection of small amounts of E. coli lipopolysaccharide (LPS) into the intercarpal joint of 5 ponies were studied. The LPS induced predictable changes all of which were analogous to acute bacterial infection, except that the development of signs occurred sooner after the LPS injection, and subsided within 36 hours. Fever was monophasic and peaked at 5-7 hours. The ponies exhibited depression, reduced or absent appetite, increased pulse and respiration rates, and lameness. The lameness became evident between 1 and 2 hours after injection, at which time warmth, articular effusion, and resentment to palpation of joint flexion were evident. Hematological changes included neutrophilic leucocytosis, and changes in copper, iron and zinc serum concentrations. The synovial fluid total protein, leucocyte, and alkaline phosphatase levels increased within 2 hours. The mucin precipitation, total protein and leucocyte counts in synovial fluid remained elevated long after clinical and hematological changes had subsided. The model is useful for the study of some aspects of infectious joint disease.
 ...
PMID:An induced synovitis disease model in ponies. 355 39

Four procedures were used to evaluate the function of polymorphonuclear leukocytes (PMN) isolated from the blood of cattle experimentally infected with bovine viral diarrhea (BVD) virus: (1) uptake of am emulsion of paraffin oil and Escherichia coli lipopolysaccharide, (2) nitroblue tetrazolium reduction, (3) chemiluminescence, and (4) iodination, or the conversion of iodide to a trichloroacetic acid-precipitable form. A marked impairment of iodination was consistently observed after infection with either a cytopathogenic or a noncytopathogenic strain of BVD virus. A corresponding decrease in paraffin oil uptake, nitroblue tetrazolium reduction, and chemiluminescence was not observed. Serum from BVD virus-infected animals did not depress iodination by normal control PMN in vitro. The iodination, procedure evaluates the activity of the myeloperoxidase, hydrogen peroxide, halide system. This system has potent bactericidal, fungicidal, and virucidal effects. The data indicate that oxidative metabolism by PMN from BVD virus-infected cattle is normal, but that the myeloperoxidase, hydrogen peroxide, halide antibacterial system is impaired. This could be explained by an inhibition of degranulation in PMN from infected cattle. The observed defect in iodination by PMN after BVD virus infection was compounded by a decrease in the number of circulating PMN. The impairment of PMN function may partially explain the increased susceptibility of cattle to secondary bacterial infection during infection with BVD virus.
 ...
PMID:Effects of bovine viral diarrhea virus infection on bovine polymorphonuclear leukocyte function. 626 88

Bacterial infection is associated with disseminated intravascular coagulation and fibrin deposition in the microcirculation; the mechanism of these effects in humans is still unclear. We have studied the generation of procoagulant activity (PCA) by cultured human endothelial cells (EC) in response to endotoxin. Cells from umbilical cord veins were grown in Eagle's minimum essential medium with 20% fetal calf serum till confluence. Absence of fibroblasts and macrophages was carefully checked. Endotoxin (Salmonella enteritidis lipopolysaccharide (LPS) W or Escherichia coli 0111:B4 LPS W, 0.01-1.0 micrograms/ml) was added to culture dishes for 4-6 h. PCA of EC was measured by a one-stage clotting assay and/or a two-stage amidolytic assay with the chromogenic substrate S-2222. In the absence of endotoxin, EC generated little, if any PCA (2-5 units/10(5) cells). In contrast, the addition of endotoxin resulted in generation of strong PCA that reached a maximum within 4-6 h (185-241 units/10(5) cells) and was dose-dependent between 1 and 0.01 microgram endotoxin/ml of culture medium. The generation of PCA required RNA and protein synthesis but did not require the presence of serum. No activity was found in the culture medium. The activity was of tissue thromboplastin type, as indicated by biological and immunological criteria. These endotoxin effects were observed in the absence of endothelial damage, as shown by phase-contrast microscopy and lack of 51Cr release. These data could contribute to elucidate the pathogenesis of vascular complications associated with endotoxemia in man.
 ...
PMID:Cultured human endothelial cells generate tissue factor in response to endotoxin. 634 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>