Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin

Costelloe, Elaine O.; Stacey, Katryn J.; Antalis, Toni M.; Hume, David

doi:10.1002/jlb.66.1.172

Cited by 43 publications

(47 citation statements)

References 51 publications

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“…TLR and IFN-␥ signaling activate different transcription factors, NF-B and IRFs versus STAT1, respectively. In addition, IFN-␥ increases expression of pathogen recognition receptors, including TLRs, and decreases the threshold concentration of MAMPs required to stimulate TLRs and induce cytokines and microbicidal activities (52,53). We postulate that IFN-␥ indirectly stimulates hemophagocy- .…”

Section: Discussionmentioning

confidence: 89%

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

et al. 2016

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During acute infection with bacteria, viruses or parasites, a fraction of macrophages engulf large numbers of red and white blood cells, a process called hemophagocytosis. Hemophagocytes persist into the chronic stage of infection and have an anti-inflammatory phenotype. Salmonella enterica serovar Typhimurium infection of immunocompetent mice results in acute followed by chronic infection, with the accumulation of hemophagocytes. The mechanism(s) that triggers a macrophage to become hemophagocytic is unknown, but it has been reported that the proinflammatory cytokine gamma interferon (IFN-␥) is responsible. We show that primary macrophages become hemophagocytic in the absence or presence of IFN-␥ upon infection with Gram-negative bacterial pathogens or prolonged exposure to heat-killed Salmonella enterica, the Gram-positive bacterium Bacillus subtilis, or Mycobacterium marinum. Moreover, conserved microbe-associated molecular patterns are sufficient to stimulate macrophages to hemophagocytose. Purified bacterial lipopolysaccharide (LPS) induced hemophagocytosis in resting and IFN-␥-pretreated macrophages, whereas lipoteichoic acid and synthetic unmethylated deoxycytidine-deoxyguanosine dinucleotides, which mimic bacterial DNA, induced hemophagocytosis only in IFN-␥-pretreated macrophages. Chemical inhibition or genetic deletion of Toll-like receptor 4, a pattern recognition receptor responsive to LPS, prevented both Salmonella-and LPS-stimulated hemophagocytosis. Inhibition of NF-B also prevented hemophagocytosis. These results indicate that recognition of microbial products by Toll-like receptors stimulates hemophagocytosis, a novel outcome of prolonged Toll-like receptor signaling, suggesting hemophagocytosis is a highly conserved innate immune response.

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Section: Discussionmentioning

confidence: 89%

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

et al. 2016

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“…It is the gene encoding plasminogen activator inhibitor type 2 (PAI-2), a member of the serine proteinase inhibitor (serpin) genes that exhibit inhibition toward the urokinase-type plasminogen activator (31). PAI-2 is detected mainly in monocyte/macrophage and modulates their functions such as inhibition of apoptosis and altered expression of the adhesion molecule and DAF (31)(32)(33). Because neutrophils express PAI-2 as well as monocytes in the inflammatory state and contribute to the persistence of fibrin and localization of infection (34), these roles of PAI-2 in inflammation possibly result in a more efficient presentation of MPO as an autoantigen in this cytokine milieu.…”

Section: Discussionmentioning

confidence: 99%

Genetic Dissection of Vasculitis, Myeloperoxidase-Specific Antineutrophil Cytoplasmic Autoantibody Production, and Related Traits in Spontaneous Crescentic Glomerulonephritis-Forming/Kinjoh Mice

Hamano

Tsukamoto

Abe

et al. 2006

The Journal of Immunology

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The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse is a model of human crescentic glomerulonephritis and vasculitis associated with the production of the myeloperoxidase (MPO)-specific antineutrophil cytoplasmic autoantibody (MPO-ANCA). Although the disease is mediated initially by mutation of the Fas gene (lpr), SCG/Kj mice also have non-Fas predisposing genetic factors. To define these factors, genome-wide quantitative trait locus (QTL) mapping was performed on female (B6× SCG/Kj) F2 intercross mice. Fourteen non-Fas QTLs were identified. QTLs of glomerulonephritis were located on chromosomes 1, 10, 13, 16, and 17, vasculitis on chromosomes 1 and 17, splenomegaly on chromosome 1, hypergammaglobulinemia on chromosomes 1, 2, 4, 6, 7, 11, 13, and 17, antinuclear Ab on chromosomes 1, 8, 10, and 12, and MPO-ANCA production on chromosomes 1 and 10. Significant QTLs derived from SCG/Kj on chromosomes 1, 2, 7, and 13 were designated Scg-1 to Scg-5, respectively, and those derived from B6 on chromosomes 4, 6, 17, and 10 were designated Sxb-1 to Sxb-4, respectively. Two loci linked to MPO-ANCA production on chromosomes 1 and 10 were designated Man-1 and Man-2 (for MPO-ANCA), respectively. Although both Scg-1 and Scg-2 were on chromosome 1 and shared several functions, it was of interest that aberrant MPO-ANCA production was exclusively controlled by Man-1, the centromeric half region of the Scg-2 chromosomal segment. We also examined the epistatic effects between the lpr mutation and non-Fas susceptibility genes. QTLs are discussed in relation to previously described loci, with emphasis on their candidate genes.

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“…In addition, it demonstrates that it is important to investigate the dose-response relationships of different oligonucleotides on each effector function. Such dose-response curves must be repeated for different effector functions, since each inducible gene may have its own characteristic dose-response relationship, as observed with LPS [56].…”

Section: Down-modulation Of the Csf-1 Receptor By Cpg Dnamentioning

confidence: 99%

The actions of bacterial DNA on murine macrophages

Sester

Stacey

Sweet

et al. 1999

Journal of Leukocyte Biology

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Murine macrophages are able to distinguish bacterial from mammalian DNA. The response is mimicked by single-stranded oligonucleotides containing unmethylated CG dinucleotides (''CpG'' motifs) in specific sequence contexts. The dose-response curve for activation is influenced by variation in the sequence flanking the core CpG motif. CpG or bacterial DNA activates several signaling pathways in common with bacterial lipopolysaccharide (LPS), leading to induction of cytokine genes such as tumor necrosis factor ␣. Pretreatment with LPS causes desensitization to subsequent activation by CpG DNA. Both stimuli also cause cell cycle arrest in macrophages proliferating in response to the macrophage growth factor colonystimulating factor-1 (CSF-1), but prevent apoptosis caused by growth factor removal. In part, cell cycle arrest by CpG DNA and LPS may be linked to rapid down-modulation of the CSF-1 receptor from the cell surface, a response that occurs in an all-or-nothing manner. The response of macrophages to CpG DNA has aspects in common with the DNA damage response in other cell types, which may provide clues to the underlying mechanism. J. Leukoc. Biol. 66: 542-548; 1999.

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Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin

Cited by 43 publications

References 51 publications

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

Genetic Dissection of Vasculitis, Myeloperoxidase-Specific Antineutrophil Cytoplasmic Autoantibody Production, and Related Traits in Spontaneous Crescentic Glomerulonephritis-Forming/Kinjoh Mice

The actions of bacterial DNA on murine macrophages

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