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)

To determine directly whether B cell precursors of adult origin are capable of generating CD5+ B cells, we reconstituted neonatal C3H. SCID mice with adult C57BL/6 bone marrow and analyzed splenic B cells 10 months later. Surface staining and flow cytometry revealed that the B cells were of donor origin and that 30% were CD5+. This confirms that in vivo generated CD5+ B cells can be adult derived. After anti-IgM (but not lipopolysaccharide) stimulation in vitro, virtually all of the B cells from the bone marrow-reconstituted mice expressed surface CD5. Sequence analysis of expressed VHDJH genes from the CD5+ B cells present after anti-IgM stimulation revealed a high frequency of N nucleotide addition in CDR3 regions. The presence of N nucleotides indicates that these sequences were derived from CD5+ B cells of adult origin rather than from long-lived fetal precursor B cells present in either the adult bone marrow at the time of transfer or adult spleen. These experiments demonstrate conclusively that adult bone marrow contains precursors for CD5+ B cells and that unlike fetal liver-derived precursors these express terminal deoxynucleotidyl transferase.
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PMID:Adult bone marrow contains precursors for CD5+ B cells. 889 71

It has been demonstrated previously that the inducible isoform of nitric oxide synthase (iNOS) is present throughout the intestinal tract in various inflammatory disease processes. Here we demonstrate that iNOS mRNA is present in the ileum but not in the jejunum or colon of normal mice. By Western blot analysis, iNOS protein is also detected in normal ileum, but not in the normal jejunum. However, by 3 h postinjection of 0.5 mg/kg lipopolysaccharide (LPS), iNOS mRNA is also detectable in the jejunum and colon. The enzyme message and protein, localized immunohistochemically by in situ hybridization and iNOS expression, is normally restricted to the villus epithelial cells. The iNOS mRNA was also present in the ilea of mice with defined intestinal flora (anaerobes only), germ-free mice, nude mice, and to a lesser extent in mice with severe combined immunodeficiency. These results suggest that the constitutive presence of iNOS in ileal epithelium indicates a role for this enzyme in maintaining intestinal homeostasis.
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PMID:Constitutive expression of inducible nitric oxide synthase in the mouse ileal mucosa. 912 64

In this study, we endeavored to determine the effectiveness of interferon beta (IFNbeta) gene therapy against highly metastatic murine UV-2237m fibrosarcoma cells. UV-2237m cells were engineered to produce murine IFNbeta constitutively following infection by a retroviral vector harboring the murine IFNbeta gene. Parental (UV-2237m-P), control-vector-transduced (UV-2237m-Neo), and IFNbeta-transduced (UV-2237m-IFNbeta) cells were injected subcutaneously (s.c.) or intravenously (i.v.) into syngeneic mice. Parental and control-transduced cells produced rapidly growing tumors, whereas IFNbeta-transduced cells did not. The tumorigenicity of IFNbeta-sensitive or -resistant parental cells was significantly suppressed when they were injected s.c. together with IFNbeta-transduced cells. The IFNbeta-transduced cells did not inhibit growth of parental cells injected s.c. at a distant site. UV-2237m-IFNbeta cells produced s.c. tumors in nude, SCID/Beige, and natural killer(NK)-cell-compromised syngeneic mice. The IFNbeta-transduced cells were more sensitive to in vitro splenic cell-mediated lysis than were the parental or control-transduced cells. Pretreatment of C3H/HeN mice with the NK-cell-selective antiserum (anti-asialoGM1) partially abrogated the cytotoxic activity of the cells. Cytotoxic activity was not observed in mixed culture of UV-2237m-IFNbeta cells and splenic cells from SCID/Beige mice. Significant cytotoxicity against UV-2237m-IFNbeta cells was mediated by macrophages activated by either IFNgamma, lipopolysaccharide, or a combination of both. Our data led us to conclude that the constitutive expression of IFNbeta can suppress tumorigenicity and metastasis of UV-2237m cells, which is due, in part, to activation of host effector cells.
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PMID:Suppression of tumorigenicity and metastasis in murine UV-2237 fibrosarcoma cells by infection with a retroviral vector harboring the interferon-beta gene. 962 37

The antibacterial effect of a soluble pectin polysaccharide, PMII, isolated from the leaves of Plantago major, was examined in inbred NIH/OlaHsd and Fox Chase SCID mice experimentally infected with Streptococcus pneumoniae serotype 6B. Serotype 6B is known to give a more protracted infection when injected intraperitoneally into susceptible mice than more virulent serotypes like type 4. PMII was administered i.p. either once 3 days before challenge or once to thrice from 3 to 48 h after challenge. The number of bacteria in blood and the mouse survival rate were recorded. Pre-challenge administration of PMII and also lipopolysaccharide (LPS), included as a control, gave a dose-dependent protective effect against S. pneumoniae type 6B infection. However, injection of PMII after establishment of the infection in NIH/OlaHsd mice had no effect. The data demonstrate that, firstly, the polysaccharide fraction PMII from P. major protects against pneumococcal infection in mice when administered systemically prechallenge, and secondly that the protective effect is owing to stimulation of the innate and not the adaptive immune system.
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PMID:Protective effect of Plantago major L. Pectin polysaccharide against systemic Streptococcus pneumoniae infection in mice. 1101 5

Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica are closely related subspecies that cause respiratory tract infections in humans and other mammals and express many similar virulence factors. Their lipopolysaccharide (LPS) molecules differ, containing either a complex trisaccharide (B. pertussis), a trisaccharide plus an O-antigen-like repeat (B. bronchiseptica), or an altered trisaccharide plus an O-antigen-like repeat (B. parapertussis). Deletion of the wlb locus results in the loss of membrane-distal polysaccharide domains in the three subspecies of bordetellae, leaving LPS molecules consisting of lipid A and core oligosaccharide. We have used wlb deletion (Deltawlb) mutants to investigate the roles of distal LPS structures in respiratory tract infection by bordetellae. Each mutant was defective compared to its parent strain in colonization of the respiratory tracts of BALB/c mice, but the location in the respiratory tract and the time point at which defects were observed differed significantly. Although the Deltawlb mutants were much more sensitive to complement-mediated killing in vitro, they displayed similar defects in respiratory tract colonization in C5(-/-) mice compared with wild-type (wt) mice, indicating that increased sensitivity to complement-mediated lysis is not sufficient to explain the in vivo defects. B. pertussis and B. parapertussis Deltawlb mutants were also defective compared to wt strains in colonization of SCID-beige mice, indicating that the defects were not limited to interactions with adaptive immunity. Interestingly, the B. bronchiseptica Deltawlb strain was defective, compared to the wt strain, in colonization of the respiratory tracts of BALB/c mice beginning 1 week postinoculation but did not differ from the wt strain in its ability to colonize the respiratory tracts of B-cell- and T-cell-deficient mice, suggesting that wlb-dependent LPS modifications in B. bronchiseptica modulate interactions with adaptive immunity. These data show that biosynthesis of a full-length LPS molecule by these three bordetellae is essential for the expression of full virulence for mice. In addition, the data indicate that the different distal structures modifying the LPS molecules on these three closely related subspecies serve different purposes in respiratory tract infection, highlighting the diversity of functions attributable to LPS of gram-negative bacteria.
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PMID:Multiple roles for Bordetella lipopolysaccharide molecules during respiratory tract infection. 1108 87

The generalized Shwartzman reaction in mice which had been primed and challenged with lipopolysaccharide (LPS) depends on interleukin (IL)-12-induced interferon (IFN)-gamma production at the priming stage. We examined the involvement in the priming mechanism of the unique population of Valpha14 natural killer T (NKT) cells because they promptly produce IFN-gamma after IL-12 stimulation. We report here that LPS- or IL-12-primed NKT cell genetically deficient mice were found to be resistant to LPS-elicited mortality. This outcome can be attributed to the reduction of IFN-gamma production, because injection of recombinant mouse IFN-gamma, but not injection of IL-12, effectively primed the NKT cell-deficient mice. However, priming with high doses of LPS caused mortality of severe combined immunodeficiency, NKT cell-deficient, and CD1-deficient mice, indicating a major contribution of NKT cells to the Shwartzman reaction elicited by low doses of LPS, whereas at higher doses of LPS NK cells play a prominent role. These results suggest that the numerically small NKT cell population of normal mice apparently plays a mandatory role in the priming stage of the generalized Shwartzman reaction.
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PMID:Resistance of natural killer T cell-deficient mice to systemic Shwartzman reaction. 1110 6

The superantigenic function of toxic shock syndrome toxin 1 (TSST-1) is generally regarded as an important determinant of its lethal effects in humans or experimental animals. This study examined the role of superantigenicity in a BALB/c mouse model of lethal TSST-1-induced hypersensitivity to lipopolysaccharide (LPS). In this model, TSST-1 greatly potentiated both LPS-induced lethality, as well as LPS-induced serum tumor necrosis factor alpha (TNF-alpha) activity. Although BALB/c-SCID mice were resistant to these LPS enhancement effects of TSST-1, BALB/c-SCID mice reconstituted with T cells were completely susceptible to the enhancement effect of TSST-1 on LPS-induced serum TNF-alpha. Mice pretreated with cyclosporine (Cs) or neutralizing antibodies against gamma interferon (IFN-gamma) did not develop lethal LPS hypersensitivity when injected with TSST-1, and these agents reduced the enhancement effect of TSST-1 on LPS-induced serum TNF-alpha by 99 and 85%, respectively. Cs pretreatment also completely inhibited the known capacity of TSST-1 to amplify LPS-induced levels of IFN-gamma in serum. In contrast, mice given Cs after a priming injection of TSST-1, but before LPS, still exhibited lethal hypersensitivity to LPS. Cs given after TSST-1 also did not inhibit enhancement of LPS-induced serum TNF-alpha by TSST-1 but inhibited the enhancement effect of TSST-1 on LPS-induced serum IFN-gamma by 50%. These experiments support the theory that TSST-1-induced hypersensitivity to LPS is mediated primarily by IFN-gamma derived from superantigen-activated T cells.
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PMID:Role of T cells and gamma interferon during induction of hypersensitivity to lipopolysaccharide by toxic shock syndrome toxin 1 in mice. 1117 86

Nonobese diabetic (NOD) mice carrying a transgenic TCR from an islet Ag-specific CD4 T cell clone, BDC2.5, do not develop diabetes. In contrast, the same transgenic NOD mice on the SCID background develop diabetes within 4 wk after birth. Using a newly developed mAb specific for the BDC2.5 TCR, we examined the interaction between diabetogenic T cells and regulatory T cells in NOD.BDC transgenic mice. CD4 T cells from NOD.BDC mice, expressing high levels of the clonotype, transfer diabetes to NOD.SCID recipients. In contrast, CD4 T cells expressing low levels due to the expression of both transgenic and endogenous TCR alpha-chains inhibit diabetes transfer. The clonotype-low CD4 T cells appear late in the ontogeny in the thymus and peripheral lymphoid organs, coinciding with resistance to cyclophosphamide-induced diabetes. These results demonstrate that diabetic processes in NOD.BDC mice are regulated by a balance between diabetogenic T cells and regulatory T cells. In the absence of specific manipulation, regulatory T cell function seems to be dominant and mice remain diabetes free. Understanding of mechanisms by which regulatory T cells inhibit diabetogenic processes would provide means to prevent diabetes development in high-risk human populations.
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PMID:Regulation of diabetes development by regulatory T cells in pancreatic islet antigen-specific TCR transgenic nonobese diabetic mice. 1205 28

Mutations in the ZAP-70 protein tyrosine kinase gene result in a severe combined immunodeficiency (SCID) characterized by a selective inability to produce CD8(+) T cells and a signal transduction defect in peripheral CD4(+) cells. Transplantation of genetically modified hematopoietic progenitor cells that express the wild-type ZAP-70 gene may provide significant benefit to some of these infants. The feasibility of stem cell gene correction for human ZAP-70 deficiency was assessed using a ZAP-70 knock-out model. ZAP-70-deficient murine bone marrow progenitor cells were transduced with a retroviral vector expressing the human ZAP-70 gene. Engraftment of these cells in irradiated ZAP-70-deficient animals resulted in the development of mature CD4(+) and CD8(+) T cells. In marked contrast, both populations were absent in ZAP-70(-/-) mice undergoing transplantation with bone marrow progenitor cells transduced with a control vector. Importantly, ZAP-70-reconstituted T cells proliferated in response to T-cell receptor stimulation. Moreover, these ZAP-70-expressing T cells demonstrated a diverse T-cell receptor repertoire as monitored by the relative usage of each T-cell receptor beta chain hypervariable region subfamily. The presence of ZAP-70 in B cells did not affect either lipopolysaccharide- or lipopolysaccharide/interleukin-4-mediated immunoglobulin isotype switching. Altogether, these data indicate that retroviral-mediated gene transfer of the ZAP-70 gene may prove to have a therapeutic benefit for patients with ZAP-70-SCID.
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PMID:Reconstitution of lymphoid development and function in ZAP-70-deficient mice following gene transfer into bone marrow cells. 1214 5

Dendritic cells (DC) and T cells were generated from Ficoll separated bone marrow (BM) mononuclear cells of primary operated breast cancer patients according to new cell culture protocols. BM-DC were capable of functioning as professional antigen-presenting cells (APCs) and of inducing autologous antigen-specific memory T-cell responses to either tetanus toxoid recall antigen or to breast cancer antigens. Treatment with lipopolysaccharide (LPS) resulted in phenotypic and functional maturation of BM-DC. When BM-DC, pulsed with breast cancer-associated tumor antigens, were cocultured with autologous patient-derived BM-T cells to allow for cognate breast cancer antigen recognition and stimulation, apoptosis of T cells-which occurred in noncognate coculture systems-was inhibited. Furthermore, in cocultures allowing for antigen-specific cognate interactions, the expression on BM-DC of CD83, MHC class II, CD40 and CD86 molecules was upregulated and the cytokines IL-12 and IFN-alpha were produced in significantly elevated amounts. Adoptive transfer of breast cancer-reactive memory T cells together with APCs into human breast cancer-bearing NOD/SCID mice caused a regression of the tumor and prolonged survival of the animals. This was not the case when such animals had been treated by transfer of reactivated BM T cells without BM-DCs. Our findings suggest that cognate interactions between cancer patient-derived memory BM-T cells and tumor antigen-presenting BM-DCs are important for reciprocal cell stimulation, survival and therapeutic activity.
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PMID:Cognate interactions between memory T cells and tumor antigen-presenting dendritic cells from bone marrow of breast cancer patients: bidirectional cell stimulation, survival and antitumor activity in vivo. 1245 56


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