Murine Bactericidal/Permeability-Increasing Protein Inhibits the Endotoxic Activity of Lipopolysaccharide and Gram-Negative Bacteria

Wittmann, Irene; Schönefeld, Marc; Aichele, Diana; Groer, Gerhard J.; Gessner, André; Schnare, Markus

doi:10.4049/jimmunol.180.11.7546

Cited by 35 publications

(35 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both bind to bacterial lipopolysaccharide (LPS) and elicit immune responses by presenting LPS to CD14 and TLR4 and signaling the acute-phase immunological response (Muta and Takeshige 2001). Bpi acts as an endogenous antibiotic protein with potent killing activity against gram-negative bacteria (Wittmann et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Genetic and environmental control of host-gut microbiota interactions

et al. 2015

View full text Add to dashboard Cite

Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut microbiota using 16s rRNA gene sequencing in a panel of 110 diverse inbred strains of mice. This panel has previously been studied for a wide range of metabolic traits and can be used for high-resolution association mapping. Using a SNPbased approach with a linear mixed model, we estimated the heritability of microbiota composition. We conclude that, in a controlled environment, the genetic background accounts for a substantial fraction of abundance of most common microbiota. The mice were previously studied for response to a high-fat, high-sucrose diet, and we hypothesized that the dietary response was determined in part by gut microbiota composition. We tested this using a cross-fostering strategy in which a strain showing a modest response, SWR, was seeded with microbiota from a strain showing a strong response, A×B19. Consistent with a role of microbiota in dietary response, the cross-fostered SWR pups exhibited a significantly increased response in weight gain. To examine specific microbiota contributing to the response, we identified various genera whose abundance correlated with dietary response. Among these, we chose Akkermansia muciniphila, a common anaerobe previously associated with metabolic effects. When administered to strain A×B19 by gavage, the dietary response was significantly blunted for obesity, plasma lipids, and insulin resistance. In an effort to further understand host-microbiota interactions, we mapped loci controlling microbiota composition and prioritized candidate genes. Our publicly available data provide a resource for future studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic and environmental control of host-gut microbiota interactions

et al. 2015

View full text Add to dashboard Cite

show abstract

“…BPI belongs to a conserved family of lipid-transfer proteins that includes as its closest relative, the LPS-binding protein (LBP). The primary structures of human LBP and BPI are approximately 45% identical (Kirschning et al 1997b;Schumann et al 1990 (Wittmann et al 2008). BPI has proven to be protective against lethal and sub-lethal challenges with gram negative bacteria and endotoxin (Wittmann et al 2008).…”

Section: Lipopolysaccharide-binding Protein (Lbp) Lps-binding Proteimentioning

confidence: 99%

“…The primary structures of human LBP and BPI are approximately 45% identical (Kirschning et al 1997b;Schumann et al 1990 (Wittmann et al 2008). BPI has proven to be protective against lethal and sub-lethal challenges with gram negative bacteria and endotoxin (Wittmann et al 2008). Presentation of endotoxin most likely occurs with endotoxin still being an integral component of the outer membrane of gram negative bacteria.…”

Section: Lipopolysaccharide-binding Protein (Lbp) Lps-binding Proteimentioning

confidence: 99%

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Frellstedt

McKenzie

Barrett

et al. 2012

Veterinary Immunology and Immunopathology

View full text Add to dashboard Cite

Endotoxemia is responsible for severe illness in horses. Individuals can become unresponsive to the endotoxin molecule after an initial exposure; this phenomenon has been called developing a state of 'endotoxin tolerance' (ET). ET has been induced in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMCs) in vitro, and to describe the cytokine profile which is associated with the ET.Blood was collected from 6 healthy horses and PBMCs were isolated. ET was induced by culturing cells with three concentrations of endotoxin given to induce ET, and evaluated after a second dose of endotoxin given to challenge the cells. The relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative PCR.ET was induced in all cells (n=6) exposed to the 2-step endotoxin challenge. In PBMCs treated with 1.0 ng/ml of endotoxin followed by challenge with 10 ng/ml of endotoxin, the relative mRNA expression of IL-10 in tolerized cells was not different from positive control cells. In contrast, the relative mRNA expression of IL-12 in tolerized cells was decreased by 15-fold after the second endotoxin challenge compared with positive control cells.This experiment demonstrated a reliable method for the ex vivo induction of ET in equine PBMCs. A marked suppression of IL-12 production is associated with ET. The production of IL-10 was not altered in ET in our model.

show abstract

“…Recombinant murine BPI has also recently been shown to inhibit endotoxic activity of LPS and gram-negative bacteria [16]. Unlike human BPI, mouse BPI failed to kill or inhibit the growth of Pseudomonas aeruginosa, perhaps revealing species-related differences in the function of this protein.…”

mentioning

confidence: 98%