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

Several investigators have reported lipid A as the biologically active unit in the lipopolysaccharide (LPS) molecule. To determine if lipid A was responsible for the reported increases in pyruvate kinase, mice were injected with endotoxin from Salmonella typhimurium SR-11, the Re mutant of Salmonella minnesota R 595, and lipid A-bovine serum albumin conjugate. The livers were homogenized and the activity of pyruvate kinase was measured. Similar increases in enzyme were obtained with all three preparations. These data imply that the lipid portion of the LPS molecule was responsible for alterations in host enzyme activity. To further determine if the lipid portion was the active unit, a lipid-degraded endotoxin (endotoxoid) prepared by potassium methylate treatment was inoculated into mice. An initial increase in liver pyruvate kinase activity was observed with all preparations. The marked increase observed at 16 h with the native product and lipid A conjugate was not obtained with the endotoxoid. These experiments extend and confirm previous observations that lipid A is responsible for the effects associated with LPS. Animals tolerant to endotoxin from S. typhimurium SR-11 were challenged with endotoxin from the Re mutant. A significant increase in pyruvate kinase activity was not obtained, suggesting that anti-O antibodies are not important in the development of tolerance.
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PMID:Effect of lipopolysaccharide and lipid A on mouse liver pyruvate kinase activity. 110 89

The effect of human plasma, the plasma protein fractions of Cohn, and crystallized serum albumin on the in vitro growth of human lymphocytes activated by concanavalin A (Con A) or bacterial lipopolysaccharide was compared. It was found that fraction V or serum albumin (SA) is essential for growth of activated T and B lymphocytes. The other plasma proteins have no effect. The growth response of Con A-activated T lymphocytes to increasing concentrations of SA is similar to the response to increasing equivalent concentrations of plasma suggesting but not proving that SA is the only growth-stimulating factor in plasma when added to a protein-free culture medium. The growth-promoting effect of SA is not due to the fatty acids or hormones bound to SA but is attributed to the albumin molecule itself or to a factor tightly bound to it. SA can also effectively replace plasma to stimulate proliferation of lymphocytes activated by allogeneic lymphocytes or purified protein derivative of tuberculin.
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PMID:Serum albumin is essential for in vitro growth of activated human lymphocytes. 117 92

Naegleria fowleri, which produces a fatal meningoencephalitis in humans, is also able to produce a progressive and fatal disease in mice. The course of the disease in DUB/ICR mice is dependent upon the infecting dose of organisms, whether administered intraperitoneally (i.p.) or intravenously (i.v.). All of the mice receiving 10(7) trophozoites/mouse i.v. or 4.85 X 10(7) trophozoites/mouse i.p. were killed within 10 days. Escherichia coli O26:B6 lipopolysaccharide, administered at a dose of 1 mg/kg 24 h prior to N. fowleri, afforded some protection for several days after challenge, but by day 8 there was no difference in survival of untreated and endotoxin-treated mice. No significant protection was afforded by a complex of lipid A with concanavalin A (ConA) or bovine serum albumin (BSA) or by dimethylmyristamide-BSA, dimethylmyristamide, BSA, beta-hydroxymyristic acid-ConA, beta-hydroxymyristic acid, ConA, myristic acid-BSA, or myristic acid. Mice surviving primary i.v. or i.p. challenge doses of N. fowleri, 5 X 10(6) and 10(7) trophozoites/mouse, respectively, were highly resistant to rechallenge with an i.v. dose of organisms (5 X 10(6) Naegleria/mouse) that produced uniformly fatal disease in untreated control mice.
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PMID:Modification of resistance of mice to Naegleria fowleri infections. 127 Jan 45

Adult C57BL/6 mice were injected with 100 micrograms of soluble, freshly deaggregated human serum albumin (HSA) to produce partial immunologic tolerance. Uninjected normal control (N) mice contain only approximately 100 B cells in their spleens with the capacity to (i) be activated in vitro into clonal proliferation by Escherichia coli lipopolysaccharide plus interleukins 2, 4, and 5, (ii) form IgG1 as well as IgM antibody, and (iii) display specificity for HSA when only IgG1 is allowed to score in an enzyme-linked immunosorbent assay (ELISA). Such N mice generate approximately 50,000 clonable anti-HSA IgG1 antibody-forming cell precursors in their spleens after T-dependent immunization with HSA absorbed onto alum and given with Bordetella pertussis adjuvant. Mice preinjected with soluble HSA (TOL) generate far fewer anti-HSA IgG1 antibody-forming cell precursors, termed anti-HSA memory cells. Splenocytes were transferred from N or TOL mice into lethally irradiated syngeneic recipients together with syngeneic bone marrow. Whereas N splenocytes generated plentiful memory cells within 2 weeks in antigenically challenged recipients, TOL splenocytes did not. Work with Ly-5 congenic mice ruled out memory cell generation from either the host or the bone marrow inoculum within this limited time. N T cells plus TOL B cells showed consistently lowered memory cell generation. TOL T cells plus N B cells showed an even greater lowering of adoptive memory cell generation. Thus the lowered response capacity of TOL mice resided in the T- and B-cell compartments. Attempts to show a suppressor component within the T-cell population were inconclusive, but a profound defect in capacity to respond to HSA in vitro was exhibited by the CD4+ T cells of TOL mice. B lymphocytes were harvested from T-dependently immunized mice 5 days after challenge, incubated with soluble HSA for 18 hr, and then adoptively transferred together with N T cells. The recently activated B cells were not rendered tolerant by this manipulation. The results argue for a major T-cell component in the process whereby soluble protein antigens ablate affinity maturation and memory cell generation.
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PMID:Memory cell generation ablated by soluble protein antigen by means of effects on T- and B-lymphocyte compartments. 134 66

Thioglycollate-induced murine C57BL/6 and C3H/HeN peritoneal macrophages synthesized interferon-beta (IFN-beta) in response to exposure to glycoproteins such as horseradish peroxidase (HRP) or mannosyl or fucosyl bovine serum albumin (BSAman of BSAfuc, respectively), but not glucosylated or galactosylated BSA (BSAglu or BSAgal, respectively). These results suggest participation of the mannosyl-fucosyl receptor (MFR) in this response. IFN synthesis was augmented by culturing macrophages in L cell-conditioned medium prior to exposure to these substances. Macrophages obtained from lipopolysaccharide (LPS)-resistant C3H/HeJ mice did not produce IFN in response to HRP. Furthermore, IFN-induction by HRP was blocked by polymyxin B. In addition, exposure of macrophages to HRP or BSAman induced cytotoxicity against NIH 3T12 cells. Cytotoxicity was not inhibited by the presence of anti-IFN-alpha/beta. In contrast to IFN induction, however, macrophages activation was LPS-independent, since this activity was demonstrated in macrophages from C3H/Hej mice. The carbohydrate specificity of these responses suggests that the MFR or an another scavenger receptor may be involved in the responses to these substances, and that cytotoxicity and IFN-induction by glycoproteins follow unique pathways.
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PMID:Induction of interferon synthesis and cytotoxicity by murine peritoneal macrophages exposed to glycoprotein ligands. 136 22

The tetrasaccharide 3-deoxy-alpha-D-manno-2-octulosonic acid (alpha-KDO) (2----8)-alpha-KDO(2----4)-alpha-KDO(2----6)-beta GlcNAc, a partial structure of chlamydial lipopolysaccharide (LPS) representing a genus-specific epitope, was synthesized and covalently linked to bovine serum albumin, resulting in an artificial glycoconjugate antigen. Mice were immunized with the glycoconjugate to prepare chlamydia-specific monoclonal antibodies. They were selected with chlamydia-specific LPS antigens and the structurally and antigenically related Re-type LPS of a Salmonella minnesota rough mutant. Characterization of the selected antibodies was by (i) hemagglutination of sheep erythrocytes coated with recombinant chlamydia-specific LPS, (ii) inhibition by synthetic polyacrylamide derivatives containing the genus-specific epitope or partial structures thereof, (iii) enzyme immunoassay with recombinant LPS and synthetic bovine serum albumin glycoconjugates as solid-phase antigens, (iv) immunofluorescence of L929 monolayers infected with Chlamydia psittaci or C. trachomatis, and (v) Western immunoblots with glycoconjugates and LPS as the antigen. Two groups of monoclonal antibodies were obtained; the monoclonal antibodies in one group cross-reacted with chlamydial and Re-type LPS, but those of the other group were chlamydia specific. Among the latter, KDO trisaccharide-specific antibodies that had the same epitope specificity as antibodies obtained after immunization with chlamydial elementary bodies were identified; however, they exhibited a more than 100-fold higher affinity. In addition, antibodies that bound preferentially to the 2.8-linked KDO disaccharide were detected, although with lower affinity. The data show that the artificial glycoconjugate antigen is similar to its natural counterpart.
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PMID:A synthetic glycoconjugate representing the genus-specific epitope of chlamydial lipopolysaccharide exhibits the same specificity as its natural counterpart. 137 90

Because subunit vaccines may create artificial epitopes, the goal of this study was to concentrate the immune response toward protective epitopes contained in a peptide, [(NAGG)5]Y. This peptide consisted of five repeat sequences of the immunodominant epitope of the circumsporozoite protein of the simian malaria parasite Plasmodium cynomolgi and a terminal tyrosine. It was conjugated to bovine serum albumin and mixed with various adjuvant formulations, including block copolymers L121, L141, L180.5 and a lipopolysaccharide (LPS). Outbred mice were vaccinated with seven vaccine formulations. Postvaccination sera from each group of mice were then pooled, and antibody responses against peptide [(NAGG)5]Y or (NAGG)5 were tested in an enzyme-linked immunosorbent assay and against sporozoites of P. cynomolgi in an indirect fluorescent antibody assay. Although all groups elicited a high antibody response to the peptide [(NAGG)5Y], the presence of the tyrosine induced a different antibody response to the peptide (NAGG)5, and formulations containing LPS alone did not induce an antibody response to either (NAGG)5 or P. cynomolgi sporozoites. The formulation including both LPS and the copolymer L121 was the only one to inhibit the development of P. cynomolgi sporozoites in rhesus monkey hepatocytes by 50%. These results suggest that vaccine formulations influence B-cell epitope selection.
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PMID:Effect of adjuvant formulations on the selection of B-cell epitopes expressed by a malaria peptide vaccine. 137 51

The humoral immune response of inbred mice to immunization with the glucuronoxylomannan (GXM) of Cryptococcus neoformans was investigated both serologically and in plaque-forming cells (PFCs). The T-helper-cell-independent quality of the GXM was demonstrated by using BALB/c nu/nu mice. Primary and secondary dose responses to three antigenic forms of GXM, (i) the native antigen, (ii) a GXM-bovine serum albumin protein conjugate, and (iii) a cryptococcal whole-cell vaccine, revealed a lack of isotype class switching and anamnestic responses. Both the levels of complement-fixing anti-GXM antibody in serum and the PFC responses in the athymic mice showed no significant differences from those in the wild-type controls. However, T cells are involved in the suppression of the primary response to GXM. When BALB/cBy mice were given rabbit anti-mouse thymocyte serum along with 0.5 microgram of GXM, both antibody levels in serum and PFC responses were significantly increased over those of control mice that received GXM and normal rabbit serum. In addition, T cells were also shown to enhance the primary immune response to GXM. BALB/cBy mice were given GXM and anti-mouse thymocyte serum on day 1. On day 2, the experimental group was given anti-mouse thymocyte serum and the control group was given saline. On day 5, comparison of the PFC responses and anti-GXM antibody titers of the two groups revealed a significant increase in the immune response of the control over the experimental group. The type 2 T-cell-independent quality of GXM was also demonstrated in CBA/cHN xid mice. These mice lack the Lyb+ subset of B cells and are unable to respond to type 2 T-independent antigens but respond normally to type 1 T-independent antigens. Type III pneumococcal polysaccharide, a type 2 T-independent antigen, was used as a negative control, and trinitrophenyl-lipopolysaccharide, a type 1 T-independent antigen, was used as a positive control. The CBA/cHN xid mice failed to respond to either type III pneumococcal polysaccharide or GXM but did not respond to immunization with trinitrophenyl-lipopolysaccharide. BALB/cBy mice responded normally to all three antigens.
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PMID:The glucuronoxylomannan of Cryptococcus neoformans serotype A is a type 2 T-cell-independent antigen. 139 21

Pulmonary surfactant has been shown to play an increasingly important role in bacterial clearance at the alveolar surface in the lung. This study describes a bactericidal mechanism in which ovine pulmonary surfactant induces killing of Pasteurella haemolytica by normal serum. To demonstrate killing, six bacterial species were incubated first with pulmonary surfactant for 60 min at 37 degrees C and then with serum for an additional 60 min at 37 degrees C. P. haemolytica type A1 strains 82-25 and L101, a P. haemolytica type 2 strain, Escherichia coli, and Klebsiella pneumoniae were susceptible and Pasteurella multocida, Serratia marcescens, and Pseudomonas aeruginosa were not susceptible to killing by ovine pulmonary surfactant and normal serum. No bacteria incubated with bovine pulmonary surfactant were killed by normal serum. Although the species origin of pulmonary surfactant was selective, the species origin of serum was not. P. haemolytica incubated with ovine pulmonary surfactant was killed by fetal calf serum, gnotobiotic calf serum, pooled normal sheep serum, pooled normal rabbit serum, and pooled guinea pig serum. Ultrastructurally, killed P. haemolytica suspensions contained dead cells and cells distorted with vacuoles between the cytoplasmic membrane and the cytoplasm. The mechanism of killing did not correlate with concentrations of complement or lysozyme or titers of residual antibody in either the pulmonary surfactant or the serum, and killing was reduced by preincubation of surfactant with P. haemolytica lipopolysaccharide. Preliminary characterization of both surfactant and serum implicate a low-molecular-weight proteinaceous component in the surfactant and serum albumin in the serum. This mechanism may help clear certain gram-negative bacteria from the lungs of sheep as a part of the pulmonary innate defense system.
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PMID:Ovine pulmonary surfactant induces killing of Pasteurella haemolytica, Escherichia coli, and Klebsiella pneumoniae by normal serum. 145 51

The inhibitory effect of beta-alanyl-L-histidinato zinc (AHZ) on bone resorption in tissue culture was investigated. Calvaria were removed from weanling rats (3-week-old male) and cultured for periods up to 48 h in Dulbecco's modified Eagle medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained 10(-7) to 10(-4) mol/l AHZ. The bone-resorbing factors, parathyroid hormone (1-34) (PTH; 10(-7) mol/l), prostaglandin E2 (10(-5) mol/l), interleukin-1 alpha (IL1 alpha; 50 U/ml), and lipopolysaccharide (10 micrograms/ml), caused a significant decrease in bone calcium content. The decreases in bone calcium content induced by bone-resorbing factors were completely inhibited by the coexistence of AHZ (10(-6) to 10(-4) mol/l). Also, AHZ (10(-5) mol/l) completely inhibited the PTH (10(-7) mol/l) or IL1 alpha (50 U/ml)-induced increase in medium glucose consumption and lactic acid production by bone tissue. Furthermore, AHZ (10(-5) mol/l) fairly blocked both PTH (10(-7) mol/l)-increased acid phosphatase and decreased alkaline phosphatase activities of bone tissue. The inhibitory effect of AHZ (10(-5) mol/l) on PTH (10(-7) mol/l)-stimulated bone resorption was clearly prevented by the presence of 10(-4) mol/l dipicolinate, a chelator of zinc. However, zinc sulfate (10(-7) to 10(-4) mol/l) did not inhibit the PTH (10(-7) mol/l)-stimulated bone resorption in tissue culture. These findings indicate that AHZ had a direct inhibitory effect on bone resorption in vitro, and the AHZ effect was found in the chemical form of zinc-chelated dipeptide.
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PMID:Inhibitory effect of beta-alanyl-L-histidinato zinc on bone resorption in tissue culture. 146 76


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