Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T helper cells reactive to myelin basic protein are clearly implicated in the pathogenesis of murine EAE. We have developed a T cell line, BML-1 that (1) is reactive to the encephalitogenic amino terminal nonapeptide (1-9NAC) of MBP, (2) is I-Au restricted, and (3) induces relapsing EAE in B10.PL (H-2u) mice. Measurement of the lymphokine profile of BML-1 revealed secretion of IL-2, interferon-gamma and lymphotoxin but not IL-4. This profile is consistent with the Th1/DTH subtype. Coculture of BML-1 with MBP-primed B cells shows that BML-1 does not provide significant helper function in vitro. In addition, BML-1 secretion of interferon-gamma was found to inhibit LPS-induced anti-MBP antibody responses. This suggested that anti-MBP antibodies may not be necessary for induction of EAE. Sera from mice, in which severe disease was induced with the 1-9NAC peptide and Bordetella pertussis, showed no development of serum antibodies to MBP. These data show that MBP-reactive Th cells of the Th-1/DTH subtype can induce EAE and do not provide Th function for anti-MBP responses and that serum anti-MBP antibodies are not found in peptide 1-9NAC-induced disease. T cell lines specific for encephalitogenic epitopes and characterized for lymphokine secretion will provide a useful tool for understanding the role of T cells in the induction of EAE.
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PMID:Encephalitogenic T cells in the B10.PL model of experimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype. 247

We previously showed the importance of the 3-deoxy-D-manno-2-octulosonic acid (KDO) residue in endotoxins (lipopolysaccharides, LPS) for the induction of the synthesis and release of interleukin-1 (IL-1) by human monocytes. We further investigated the effect of some structural variations within the KDO molecule on IL-1 production induced by LPS. Deamination of Bordetella pertussis LPS, followed by mild anhydrous acidic methanolysis released a hexasaccharide (fragment B'), which had a terminal methyl ketoside KDO residue with a methyl-esterified carboxyl group. This fragment was unable to induce IL-1 production by human monocytes. Fragment B' could be converted into an active hexasaccharide by de-esterification (fragment B-OMe), but not by reduction of the methyl ester group. The KDO residues in the LPS of some bacterial species have been shown to be phosphorylated and we observed that these LPS were weak IL-1 inducers. Phosphorylated KDO present in Vibrio cholerae and B. pertussis LPS respond poorly in the thiobarbiturate assay (specific for KDO). However, if these LPS were dephosphorylated with aqueous hydrofluoric acid (HF) their KDO response in this assay was increased 5.4- to 2.6-fold, respectively. In parallel, the HF-treated LPS were more potent IL-1 inducers than untreated endotoxins. These data confirm that the KDO residue(s) present in all endotoxins play(s) a major role in the signal(s) leading to IL-1 production by human monocytes, and show that IL-1 induction by LPS (1) requires a free carboxyl group in the KDO and (2) is correlated with the degree of substitution of the KDO.
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PMID:Interleukin-1 induction by lipopolysaccharides: structural requirements of the 3-deoxy-D-manno-2-octulosonic acid (KDO). 254 3

Interleukin-1 (IL-1) is a putative mediator of inflammation released by activated macrophages in vitro. The IL-1 release by rat macrophages collected either from exudates in pertussis-induced air pouches or from the peritoneum during adjuvant arthritis has been investigated. In air pouch inflammation LPS-stimulated macrophages collected from sensitized animals release more IL-1 than cells from control rats at day 6 after challenge. This enhanced IL-1 release parallels the extent of mononuclear cell migration in the inflammatory lesion. In adjuvant arthritis LPS-stimulated macrophages collected from sensitized animals release more IL-1 than cells from control rats at days 16 and 23 after adjuvant injection. The secondary inflammation in arthritic rats was statistically significant at days 16 to 28. These results indicate that during immunological inflammation macrophages either from the inflamed area or from a non-inflamed region release more IL-1 than control cells. This release parallels the extent of the inflammation and may be important in its pathogenesis.
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PMID:The release of interleukin-1-like activity by macrophages in two models of immunological inflammation in the rat. 255 98

In mice, greatly enhanced susceptibility to the lethal toxicity of whole-cell pertussis vaccine (PV) was produced by agents known to induce hypersusceptibility to endotoxin (LPS). The decreases in LD50 were 100-fold, 125-fold and 16-fold with galactosamine (GalN), actinomycin D (AcD) and lead acetate (PbAc) respectively and the animals died within 1-2 days. However, these decreases were less than those observed with extracted E. coli LPS, the LD50 of which was reduced approximately 500-fold, 800-fold and 50-fold respectively by these agents. In control mice, without drugs, the main lethal factor in the PV used here seemed to be pertussis toxin (PT), since deaths occurred at 3-5 days after injection, and heating the vaccine at 80 degrees C for 30 min raised the LD50 from 4 to greater than 6 single human doses (SHD) per mouse. In GalN and PbAc-treated mice, the toxicity of PV can be explained by its LPS content in view of the failure of heating at 80 degrees C to reduce toxicity. However, in AcD-treated mice, the 80 degrees C heated vaccine was threefold less toxic than the unheated material, suggesting a contribution of PT to vaccine toxicity in these animals. Indeed the toxicity of PT was increased by AcD. The possible bearing of these observations on children who appear to show serious adverse reactions to PV is discussed. Two acellular vaccines were devoid of lethal toxicity in either normal mice or in mice treated with any of the three drugs.
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PMID:Effect of hyperreactivity to endotoxin on the toxicity of pertussis vaccine and pertussis toxin in mice. 278 57

Cell surface-specific radiolabelling techniques, monoclonal antibody analyses, and chemical and physical isolation of cell fractions were used to study the surface of B. pertussis cells. Four surface specific proteins were identified by radioiodination and monoclonal antibody techniques. These included the filamentous hemagglutinin (FHA), and three outer membrane proteins-OMP91, OMP18 and OMP15. Membrane blebs were isolated from culture supernatants and shown to contain LPSII, pertussis toxin (PT), FHA, OMP91, and OMP18, but not OMP15. The level of LPS I in blebs appeared to be reduced from the level in cell envelopes. Bleb fractions contained enzymatically active adenylate cyclase (AC), and biologically active dermonecrotic toxin (DNT) and PT. Blebs were also toxic for mice, even when heated to 80 degrees C for 30 minutes. To explain these data, we propose that membrane blebs comprise an effective toxin delivery system, and that the cell surface of B. pertussis is composed of at least two domains.
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PMID:Cell surface antigens of Bordetella pertussis. 287 98

The enzyme-linked immunosorbent assay (ELISA) has been used for the determination of the isotype and the specificity of Bordetella pertussis serum antibodies induced by natural infection and by vaccination. In a previous study (J. Med. Microbiol., 16, 417-426 (1984)) it was shown that the presence of pertussis serum IgA antibodies could be used as an indicator of infection: IgA antibodies were not induced by vaccination nor transported from the mother to the serum of the child. In the present study ELISA was used for the determination of IgA, IgM and IgG antibodies. From the results obtained with sera from suspected pertussis cases, it was concluded that antibodies against FHA are hardly induced by infection, in contrast to anti-LPF (determined in a fetuin sandwich ELISA) and anti-LPS antibodies. In view of the lower standard deviation of the mean anti-LPF antibody titer these antibodies were studied more extensively. From a number of bacteriologically proved pertussis cases, it was shown that high levels of IgG anti-LPF antibodies were found before IgA antibodies could be detected. On the other hand, we had the impression that IgG antibodies declined more rapidly than IgA antibodies. One has, however, to take into account that IgG antibodies are transferred from mother to child. From assay of sera from infants prior to, during and two months after vaccination (ages of vaccination: 3, 4, 5 and 12 months) it was concluded that IgG anti-LPF antibodies were induced to a much lower level by DTP-polio vaccination (10 O.U. per dose) than by natural infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved serodiagnosis of whooping cough caused by Bordetella pertussis by determination of IgG anti-LPF antibody levels. 287 20

Isolated and purified leucocytosis promoting factor (LPF), alternatively described as pertussis toxin, reduced the hypotension after beta 2-adrenoceptor stimulation with salbutamol as well as the negative chronotropic activity induced by the muscarinic receptor stimulant arecoline 4 days after its injection into rats. These inhibitory effects of LPF were accompanied by a reduction in basal blood pressure. No effect on autonomic responsiveness or blood pressure was observed 5 h after injection of LPF. Sublethal doses of purified B. pertussis endotoxin (LPS) elicited neither vascular beta 2-adrenergic nor cardiac cholinergic blockade 4 days following injection. Only a distinct vascular beta 2-adrenolytic effect was measured 5 h after pretreatment with the same doses of LPS. This beta 2-adrenoceptor hyporesponsiveness was accompanied by neither an anticholinergic nor a hypotensive effect, but rather by a slight but significant elevation of the blood pressure. In conclusion, both components of B. pertussis (LPS and LPF) give rise to vascular beta 2-adrenergic hyporesponsiveness irrespective of blood pressure effects. There is an important difference between both components with respect to their various kinetic profiles for this phenomenon: an early occurring and short-lasting beta 2-adrenergic blockade for LPS and a late occurring LPF-mediated beta 2-adrenergic blockade.
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PMID:Vascular beta-adrenoceptor blocking activity of endotoxin and pertussis toxin from Bordetella pertussis in rats. 287 90

Due to the formation of micelles, severance of the hydrophilic (poly- or oligosaccharide) and hydrophobic ("Lipid A") domains of bacterial lipopolysaccharides at pH 3.4 or 4.5 and 100 degrees is slow and sometimes does not proceed at all; partially degraded fragments are usually formed. At pH 3.4 (100 degrees) in aqueous 1% sodium dodecylsulphate (SDS), both lipopolysaccharides of the Bordetella pertussis endotoxin are cleaved within 20-30 min, but 80% of the glycosidically bound phosphate present in the hydrophobic domain is lost. Other endotoxins behave similarly. At pH 4.5 (100 degrees) and in the absence of detergent, hydrolysis of the glycosidic bonds of 3-deoxy-D-manno-2-octulosonic acid residues of the B. pertussis endotoxin is negligible but, in aqueous 1% SDS, severance of the two regions of LPS 1 is complete within 1 h (that of LPS-2 requires 3-4 h), and the glycosidically bound phosphate of the isolated hydrophobic region is preserved. Comparison of the rate of acid-catalysed hydrolysis of the glycosidically bound phosphate present in this "isolated Lipid A" preparation with that of 2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-alpha- and -beta-D-glucopyranose 1-phosphates established that the former 1-phosphate was the alpha anomer.
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PMID:Detergent-accelerated hydrolysis of bacterial endotoxins and determination of the anomeric configuration of the glycosyl phosphate present in the "isolated lipid A" fragment of the Bordetella pertussis endotoxin. 290 66

Analysis of the lipopolysaccharide (LPS, endotoxin) in cell sonicates of four Danish vaccine strains of Bordetella pertussis (3803, 3825, 3843 and 3860) and of purified strain 3803 LPS in sodium dodecyl sulphate-polyacrylamide gel electrophoresis by silver staining, showed identical profiles. The LPS profile revealed a dominant, brownish LPS II band and a minor, faster-migrating, black-stained LPS I band. However, the ratio of LPS I to LPS II in the preparation of purified LPS differed slightly from the cell sonicates. Using marker LPS, the molecular weights of LPS I and LPS II were estimated at 5.4 and 6.0 kD, respectively. Seven different lots of whole cell pertussis vaccine were assayed for LPS in the Limulus Amoebocyte Lysate test and were found to contain 0.9-2.8 micrograms LPS/ml. No significant difference in the content of LPS in similar dilutions of the individual strains was observed. In addition, the distribution of free and cell-bound LPS in four pertussis vaccines was investigated. Most of the LPS was found to exist as free LPS. During several months, the course of both LPS and pertussis toxin (Pt) release in freshly killed B. pertussis preparations was followed. In the first few weeks, 35-50% of the LPS was released and after 5-6 months of storage 60-80% had been released. In contrast, less than 10% of the biologically active pertussis toxin was released during the experimental period. The possibility of producing a safer whole cell pertussis vaccine by reducing the amount of free LPS without reducing the protective value correspondingly is discussed.
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PMID:Lipopolysaccharides in a traditional pertussis vaccine. 290 42

An attempt was made to identify the molecular structures that are present in bacterial LPS and induce the production of intracellular and extracellular pools of IL 1 by peritoneal macrophages of the mouse and by human monocytes. Activities of glycolipids and carbohydrates prepared by synthesis, and structurally related to the hydrophobic (Lipid A) and to the polysaccharide (PS) regions of LPS were compared with those induced by Bordetella pertussis endotoxin and by fragments derived therefrom. Both isolated regions of this LPS (PS and Lipid A) were able to induce IL 1 synthesis by monocytes and macrophages. Among the synthetic glycolipids employed, propyl-2-deoxy-2-[(3R)-3-hydroxytetrade-canamido]-4-O-pho sph ono-6-O-tetradecanoyl-beta-D-glucopyranoside (glycolipid M9) induced IL 1 secretion more efficiently than Lipid A and LPS, whereas the amounts of intracellular IL 1 produced upon induction by these three substances were comparable. Macrophages from C3H/HeJ mice were unresponsive to Lipid A and to glycolipid M9, but produced IL 1 when incubated with PS or with a hydrophilic fragment isolated after methanolysis of the endotoxin. However, all synthetic derivatives of 3-deoxy-D-manno-2-octulosonic acid (KDO) used in this study failed to induce IL 1 production by both mouse macrophages and human monocytes. The implications of these findings for a more precise comprehension of the molecular mechanism of LPS-induced activation of macrophages, and the relations between the molecular structures required for the induction of IL 1 production vs cytostatic activity in macrophages, are discussed.
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PMID:Induction by lipopolysaccharide of intracellular and extracellular interleukin 1 production: analysis with synthetic models. 349 81


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