Nramp Transfection Transfers Ity/Lsh/Bcg-Related Pleiotropic Effects on Macrophage Activation: Influence on Oxidative Burst and Nitric Oxide Pathways

Barton, Chris; Whitehead, SS; Blackwell, Jenefer M.

doi:10.1007/bf03401551

Cited by 127 publications

(95 citation statements)

References 34 publications

(41 reference statements)

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“…23 Instead, allele 7 (or the variant (GT) 11 allele) was found in both studies at a frequency of 0.032 and 0.049, respectively. It has the sequence t(gt) 5 ac (gt) 5 aT(gt) 11 ggcaga(g) 6 and differs by a single nucleotide from allele 1 (the classical (GT) 11 allele) that has the sequence t(gt) 5 ac(gt) 5 aC(gt) 11 ggcaga(g) 6 . These two alleles have the same fragment length and can easily be distinguished by restriction analysis using RsaI.…”

Section: Resultsmentioning

confidence: 77%

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Extent and distribution of linkage disequilibrium around the SLC11A1 locus

2003

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The SLC11A1 (or NRAMP1) locus on human chromosome 2q35 encodes for the protein solute carrier family 11, member 1. It is expressed in macrophages and involved in the early stages of macrophage priming and activation. Different association studies have shown that the SLC11A1 gene affects susceptibility to infectious diseases and autoimmune inflammatory diseases. Although functional SLC11A1 polymorphisms may account for its role in affecting the susceptibility to these diseases, the positive association can also be because of flanking polymorphisms showing linkage disequilibrium (LD) with this locus. This is the first systematic study to investigate the LD pattern within and around the gene. LD was investigated by genotyping 17 genetic markers in a Chinese population (n ¼ 360). The results indicate that LD is maintained at least 110 kb both upstream and downstream of the locus. The complex LD pattern demands that association studies with SLC11A1 should be carried out with both 5 0 and 3 0 markers. The strong LD between IL8RB and the 5 0 SLC11A1 markers also dictates that IL8RB be tested for association with these diseases. Thus, positive association with SLC11A1 should be interpreted cautiously, and IL8RB should also be considered as a potential candidate susceptibility gene unless proven otherwise.

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Section: Resultsmentioning

confidence: 77%

“…It was shown that Slc11a1 could regulate and act early in the macrophage activation for antimicrobial activity. [10][11][12][13] This led to the speculation that variants of human SLC11A1 might play a role in controlling resistance to some intracellular infections in humans.…”

Section: Introductionmentioning

confidence: 99%

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

2003

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“…The murine macrophage cell lines RAW 246.7, wildtype (WT) RAW 7.5R, and RAW 10S were a kind gift from J. M. Blackwell (Cambridge University, Cambridge, U.K.). The 7.5R and 10S lines are stable transfectants, the generation of which has been described previously (22). These were cultured in RPMI (Life Technologies) supplemented with 10% FCS and 2 mM glutamine.…”

Section: Cells and Bacteriamentioning

confidence: 99%

ATP-Mediated Killing of Intracellular Mycobacteria by Macrophages Is a P2X7-Dependent Process Inducing Bacterial Death by Phagosome-Lysosome Fusion

Fairbairn

Stober

Kumararatne

et al. 2001

The Journal of Immunology

217

181

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Mycobacterium tuberculosis survives within host macrophages by actively inhibiting phagosome fusion with lysosomes. Treatment of infected macrophages with ATP induces both cell apoptosis and rapid killing of intracellular mycobacteria. The following studies were undertaken to characterize the effector pathway(s) involved. Macrophages were obtained from p47phox and inducible NO synthase gene-disrupted mice (which are unable to produce reactive oxygen and nitrogen radicals, respectively) and P2X7 gene-disrupted mice. RAW murine macrophages transfected with either the natural resistance-associated macrophage protein gene 1 (Nramp1)-resistant or Nramp1-susceptible gene were also used. The cells were infected with bacille Calmette-Guérin (BCG), and intracellular mycobacterial trafficking was analyzed using confocal and electron microscopy. P2X7 receptor activation was essential for effective ATP-induced mycobacterial killing, as its bactericidal activity was radically diminished in P2X7−/− macrophages. ATP-mediated killing of BCG within p47phox−/−, inducible NO synthase−/−, and Nramps cells was unaffected, demonstrating that none of these mechanisms have a role in the ATP/P2X7 effector pathway. Following ATP stimulation, BCG-containing phagosomes rapidly coalesce and fuse with lysosomes. Blocking of macrophage phospholipase D activity with butan-1-ol blocked BCG killing, but not macrophage death. ATP stimulates phagosome-lysosome fusion with concomitant mycobacterial death via P2X7 receptor activation. Macrophage death and mycobacterial killing induced by the ATP/P2X7 signaling pathway can be uncoupled, and diverge proximal to phospholipase D activation.

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“…The actual immunological function of Nramp-1 is not clear except for some indications that it inhibits bacterial growth in reticuloendothelial tissues in an early phase of infection. The mechanism is supposed to operate by modulation of the cytocidal activity of macrophages by enhancing the production of nitric oxide, phagolysosomal fusion, cytokine production and expression of class II MHC molecules [6,46]. There is a link between Nramp-1 polymorphism and differences in mortality after salmonella infection in the chicken [57].…”

Section: Other Proteins Associatedmentioning

confidence: 99%

Immunological basis of differences in disease resistance in the chicken

Zekarias

Huurne²,

Landman

et al. 2002

Vet. Res.

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-Genetic resistance to diseases is a multigenic trait governed mainly by the immune system and its interactions with many physiologic and environmental factors. In the adaptive immunity, T cell and B cell responses, the specific recognition of antigens and interactions between antigen presenting cells, T cells and B cells are crucial. It occurs through a network of mediator proteins such as the molecules of the major histocompatibility complex (MHC), T cell receptors, immunoglobulins and secreted proteins such as the cytokines and antibodies. The diversity of these proteins that mainly is due to an intrinsic polymorphism of the genes causes phenotypic variation in disease resistance. The well-known linkage of MHC polymorphism and Marek's disease resistance difference represents a classic model revealing immunological factors in resistance differences and diversity of mediator molecules. The molecular bases in any resistance variation to infectious pathogens are vaguely understood. This paper presents a review of the major immune mediators involved in resistance and susceptibility to infectious diseases and their functional mechanisms in the chicken. The genetic interaction of disease resistance with production traits and the environment is mentioned. et les interactions entre les cellules présentant des antigènes, les cellules T et B, sont cruciales. Cela se produit à travers un réseau de protéines médiatrices telles que les molécules du complexe majeur d'histocompatibilité (CMH), les récepteurs des cellules T, les immunoglobulines et les protéines sé-crétées telles que les cytokines et les anticorps. La diversité de ces protéines, qui est surtout due au polymorphisme intrinsèque des gènes, entraîne une variation phénotypique dans la résistance aux maladies. Le lien bien connu entre le polymorphisme du CMH et les différences dans la résistance à la maladie de Marek représente un modèle classique révélant les facteurs immunologiques dans les différences de résistance et la diversité dans les molécules médiatrices. Les bases moléculaires impliquées dans toute variation de résistance aux pathogènes infectieux sont à peu près comprises. Cet article présente une synthèse sur les principaux médiateurs de l'immunité impliqués dans la résis-tance et la sensibilité aux maladies infectieuses chez le poulet et leurs mécanismes fonctionnels. L'interaction génétique entre la résistance aux maladies et les traits de production et l'environnement est mentionnée.

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Nramp Transfection Transfers Ity/Lsh/Bcg-Related Pleiotropic Effects on Macrophage Activation: Influence on Oxidative Burst and Nitric Oxide Pathways

Cited by 127 publications

References 34 publications

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

ATP-Mediated Killing of Intracellular Mycobacteria by Macrophages Is a P2X7-Dependent Process Inducing Bacterial Death by Phagosome-Lysosome Fusion

Immunological basis of differences in disease resistance in the chicken

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