Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0519030 (Klebsiella)
 21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stimulating activity of several preparations isolated from a membrane proteoglycan of a nonencapsulated smooth strain of Klebsiella pneumoniae (Kp-MPG) on the oxidative burst of human blood monocytes was assessed by luminol-enhanced chemiluminescence (CL). Five Kp derivatives were studied: a 34-kd acylpoly(1,3)galactoside (APG), obtained by drastic alkaline hydrolysis and purified by chromatography; an APG preparation subjected to acid hydrolysis that removed the core part and all fatty acids, leaving intact the galactose chain of APG (GC-APG); an APG preparation subjected to mild oxidation (ox APG); a preparation obtained by mild alkaline hydrolysis of Kp-MPG, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and a polymer of the latter compound, APG pol. EFA-APG directly stimulated monocyte CL, whereas Kp-MPG, APG pol, and the whole bacterial cells had little or no activity. APG itself and ox APG induced a weaker response than EFA-APG. Polymyxin B sulfate completely inhibited the CL response to bacterial lipopolysaccharide (LPS) but not to EFA-APG. The stimulating action of EFA-APG on blood monocytes was dependent on the extracellular levels of both calcium and magnesium. Preincubation of monocytes with monoclonal antibody anti-Mac-1 directed against CD11b, the alpha chain of complement receptor type 3 (CR3; CD11b/CD18), strongly inhibited CL activation by EFA-APG and to a lesser extent CL activation by unopsonized zymosan and rough LPS. Altogether, these findings provide indirect evidence for the contribution of the CD11b/CD18 integrin in the functional interaction of EFA-APG with monocyte membranes. They demonstrate the role of fatty acids in the triggering of monocyte oxidative burst, while the polysaccharide chain itself does not contribute to induction of the CL response in this model. In keeping with the effects of EFA-APG and APG, we show that the monocyte CL response was triggered by bacterial LPS from the rough strain of Salmonella minnesota Re 595 and its lipid A, but not by LPS from smooth strains, again suggesting a critical role for the lipid moiety.
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PMID:Activation of human monocyte chemiluminescence response by acylpoly(1,3)galactosides derived from Klebsiella pneumoniae. 143 64

The binding of a membrane proteoglycan from a non-encapsulated strain of Klebsiella pneumoniae (Kp-MPG) and four derivatives thereof, to human leukocytes, was investigated by indirect immunofluorescence using biotinylated F(ab')2 fragments of anti-Kp-MPG antibodies and the streptavidin-phycoerythrin amplification system in flow cytometry. Four Kp-MPG derivatives were studied: 1/ an acylpoly(1,3)galactoside (APG), 2/ an APG preparation submitted to acid hydrolysis which removed all fatty acids, but left intact the galactose chain of APG (GC-APG), 3/ a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG) and 4/ a polymer of the latter compound (APG pol). Kp-MPG, APG and EFA-APG were shown to bind exclusively to monocytes at the lowest concentrations (from 0.15 to 3 microM APG). At higher concentrations, these compounds interacted with polymorphonuclear leukocytes, and with lymphocyte subsets in the following decreasing order: B cells, NK cells, CD8+ and CD4+ lymphocytes. Neither APG pol or GC-APG nor K. pneumoniae smooth LPS showed significant binding to leukocytes. However Kp-LPS treated by drastic alkaline hydrolysis displayed binding properties similar to those of APG. Removal of the ester-linked C14 and C16 fatty acids from EFA-APG did not affect the binding of the molecule. The capacity of cells from the myelomonocytic lineage to bind Kp-MPG and APG was very low in phenotypically immature cell lines (HL60 and U937) as compared with monocytes or polymorphonuclear cells. Treatment of U937 cells with interferon-gamma up-regulated their APG binding capacity along with the expression of the integrin CD 11 b and the CD 14 molecule, whereas monocytes exposed to interferon-gamma showed an increased binding of APG associated with an elevated expression of the galactose specific lectin Mac-2. The data demonstrate a preferential binding of Kp-MPG and APG to cells of the monocyte/macrophage lineage. APG binding does not involve the poly (1,3) galactose chain and the ester-linked C14 and C16 fatty acids but requires the presence of the hydrophobic part of the molecule.
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PMID:Binding of a membrane proteoglycan from Klebsiella pneumoniae and its derivatives to human leukocytes. 149 Jul 26

The binding of a 34-kDa (mol. wt.) acylpoly(1,3)galactoside (APG) extracted from a membrane proteoglycan of Klebsiella pneumoniae to human blood leucocytes was investigated. APG is made of a long poly(1,3)galactose chain, a core-like region and a lipid moiety which comprises two glucosamine residues bound to a phosphate group and two beta OH myristic acids. Fluoresceinated APG was shown to bind preferentially to monocytes and to a lesser extent to polymorphonuclear neutrophils, as determined by flow cytometry. Binding of fluoresceinated APG was inhibited by unlabelled APG; it was concentration dependent, but not saturable, with rapid kinetics. It occurred at +4 degrees C but was markedly increased at 37 degrees C. It involved trypsin-sensitive molecules on the membrane of monocytes. Neither the parent proteoglycan nor lipopolysaccharide from K. pneumoniae or Salmonella minnesota competed for APG binding. A minor non-specific binding to lymphocytes, occurring predominantly on B cells, was observed. Unlike that of lipopolysaccharide, the APG binding was not blocked by polymyxin B sulphate. Interaction between the galactose chain of APG and the galactose receptor does not account for the binding of APG to monocytes because the galactose receptor (Mac-2) is expressed at high density on activated macrophages but not on monocytes. Despite its strong binding to human blood monocytes, APG displayed a much weaker activity than K. pneumoniae membrane proteoglycan with respect to induction of monocyte cytokine synthesis. When administered as a Technetium 99 conjugate, APG was shown to label inflammatory foci in experimental animals, and its property as a marker of macrophages is currently being evaluated in clinical trials.
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PMID:Binding of a bacterial acylpoly(1,3)galactoside to human blood leucocytes. 161 80

We investigated the effects of the beta-adrenoceptor agonist isoproterenol (ISO) and the alpha- and beta-adrenoceptor agonist norepinephrine (NE) on murine B-cell activation. Cells were stimulated either by anti-mouse mu-chain antibodies (anti-mu), or by lipopolysaccharide (LPS), or a membrane proteoglycan of Klebsiella pneumoniae (Kp MPG), a T-independent polyclonal activator distinct from LPS, which induces B-cell proliferation and Ig synthesis. ISO and NE enhanced LPS- and Kp MPG-induced B-cell proliferation and maturation into IgM-, IgG- and IgA-secreting cells. The enhancement was prevented by prior addition of the beta-adrenoceptor antagonist propranolol but not by the alpha-adrenoceptor antagonist phentolamine. Earlier events in the LPS- and Kp MPG-stimulated B-cell activation, such as increases in Ia antigen expression and RNA synthesis, were not modified by the catecholamines. Unlike ISO and NE, the membrane-permeant cyclic adenosine 3',5'-monophosphate (cAMP) analogue dibutyryl cAMP (dbcAMP), and the potent adenylate cyclase activator forskolin did not enhance but even inhibited DNA synthesis and Ig secretion stimulated by LPS and Kp MPG. In addition, ISO and NE did not enhance but strongly inhibited anti-mu-induced B-cell proliferation, and these effects were mimicked by dbcAMP and forskolin. Collectively, the data demonstrate that beta-agonists differently modulate B-cell activation depending upon the polyclonal activator, and provide additional evidence for distinct biochemical mechanisms of B-cell activation by anti-mu and LPS. Moreover, our results indicate that beta-adrenergic stimulation up-regulates B-cell responses to LPS and Kp MPG by a novel and cAMP-independent pathway.
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PMID:Differential regulation of mouse B-cell activation by beta-adrenoceptor stimulation depending on type of mitogens. 215 73

D53 (Immucytal) is a compositive vaccine made of immunogenic ribosomes extracted from 4 bacterial species (Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae) associated with a membrane proteoglycan from a non-encapsulated strain of Klebsiella pneumoniae (MPG-Kp). In this work we have studied the effect of the compound on human polymorphonuclear leukocyte (PMN) function "in vitro". We have demonstrated that D53 was able to significantly increase Fc- receptor dependent phagocytosis without modify the C3-receptor dependent activity. Furthermore D53 enhanced the oxidative metabolism (evaluated by chemiluminescence) both using cells in resting conditions or after stimulation with phagocytable or soluble stimuli. On the contrary D53 caused a dose-dependent inhibition of PMN migration toward different chemoattractants. Using the two constitutive fractions of the compound (ribosomes and proteoglycans) we have observed that the MPG-Kp component was mainly responsible for the modulating activity of the drug on human PMNs.
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PMID:Immunomodulation of polymorphonuclear leukocytes by D53 Immucytal and its constitutive fractions. 249 32

In this preliminary report, we describe our inability to induce IgE antibody to a well-characterized bacterial component, the membrane proteoglycan of Klebsiella pneumoniae and its major protein fraction FIII-B in BALB/c mice. In contrast, an immunomodulatory effect of membrane proteoglycan of K. pneumoniae on the IgE and IgG antibody responses to ovalbumin could be demonstrated.
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PMID:Relationship between bacteria and IgE. 265 16

RU-41740, a glycoprotein complex extracted from Klebsiella pneumoniae, is an immunomodulating agent which acts on B cells and macrophages. It has been shown that RU-41740 is composed mainly of two macromolecular fractions, F1, having an LPS-related structure, and P1, with a proteoglycan structure. In the present paper, the effects of these molecules on B cells and on IL-1 and tumour necrosis factor (TNF), production by macrophages were compared. Data reveal that both fractions were mitogenic for murine B cells and induced IL-1 and TNF production by macrophages. The LPS-like fraction (F1) was sensitive to polymyxin B and was unable to activate macrophages and spleen cells from LPS non-responder mice. The P1 fraction was mitogenic for B cells and induced the production of IL-1 and TNF activities by macrophages from LPS non-responder C3H/HeJ mice. The cytotoxic activity was due to TNF alpha, since treatment with anti-TNF alpha antiserum abrogated the lytic activity of supernatants from stimulated macrophages. The differences observed between P1 and F1 fractions in terms of sensitivity to polymyxin B and activity towards C3H/HeJ spleen cells and macrophages suggest that the two structurally distinct molecules isolated from RU-41740 could act at different sites on immunocompetent cells.
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PMID:Immunological activities of RU-41740, a glycoprotein extract from Klebsiella pneumoniae. III. Role of LPS-like and LPS-non-related molecules. 266 80

A vaccine has been prepared with ribosomes of Candida albicans serotypes a and b plus, as adjuvant, membrane proteoglycan from a nonencapsulated Klebsiella pneumoniae. A preliminary phase II trial without placebo control was conducted in 22 women with a history of frequent recurrences of vulvovaginal candidiasis (VVC). Initially, all the patients were treated locally with an antimycotic cream. Beginning at the same time, vaccine was taken orally in capsules containing 0.55 microgram active components. It was administered intermittently over six months, groups of women taking doses of two, three, six or nine capsules. Tolerance was excellent except for mild nausea, probably due to the excipients, in two patients taking nine capsules. Twenty patients completed the study. Only seven of them had a documented recurrence of VVC during the 6 months on vaccine. No recurrence occurred in the eight women taking six or nine capsules per day. Before the study, these 20 patients had had an average of 3.59 attacks of VVC per 6 months. On vaccine, the average rate of recurrence was only 0.55 attacks per 6 months. A multicentre placebo-controlled study of the efficacy of this vaccine is in progress to validate these encouraging preliminary results.
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PMID:Phase II study of D.651, an oral vaccine designed to prevent recurrences of vulvovaginal candidiasis. 268 57

The lymphocyte activating properties of a membrane proteoglycan (MPG) extracted from a mutant non-encapsulated strain of Klebsiella pneumoniae (Kp) (biotype a I-145) were investigated. Kp MPG induced a strong proliferative response of BALB/c spleen cells and Peyer's patches cells. Thymidine incorporation was dose-related (from 1 to 100 micrograms Kp MPG/ml) and reached a maximum at day 3. It was not reduced by removal of most adherent cells, nor by depletion of Thy1-2 positive cells, but it was abrogated by removal of surface immunoglobulin bearing cells. Spleen cells from nude mice and those from C3H/Hej mice were strongly stimulated by Kp MPG. Conversely Kp MPG did not induce interleukin 2 production and did not trigger the proliferation of thymocytes but stimulated interleukin 1 production by adherent spleen cells. Finally, unfractionated or B-enriched spleen cells cultured with Kp MPG synthesized IgM and, to a lesser extent, IgG and IgA. It is concluded that Kp MPG is a T-independent polyclonal B cell activator and an inducer of interleukin 1 production.
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PMID:Polyclonal activation of murine B cells by a membrane proteoglycan of Klebsiella pneumoniae. 331

Upon testing the individual fractions of a composite bacterial vaccine for biological activities, a potent immuno-stimulatory capacity could be demonstrated within a crude membrane proteoglycan preparation from Klebsiella pneumoniae. One of its characteristic features was the capacity to induce alpha-type interferon and increased NK activity in vivo in mice, following intraperitoneal or oral administration. A highly purified fraction from the crude preparation was obtained using alkaline hydrolysis, delipidation and size fractionation. This fraction was shown to be a very potent inducer of NK cells in vivo or in vitro, where in the latter systems concentrations as low as 0.1 microgramme per ml were highly efficient.
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PMID:NK-cell stimulating properties of a membrane proteoglycane from non-capsulated Klebsiella pneumoniae biotype a. 391 78


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