Recognition of Bacterial Endotoxin in the Lungs

Martin, Thomas R.

doi:10.1165/ajrcmb.23.2.f189

Cited by 111 publications

(93 citation statements)

References 53 publications

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“…There is no doubt that the down-regulation of receptors could be important for the prevention of an overwhelming release of proinflammatory cytokines, thus preventing the development of septic shock (Dobrovolskaia and Vogel, 2002). This is because, monocytes/macrophages release a spectrum of proinflammatory cytokines in response to LPS/ LBP complexes, including tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8, to initiate host defense (Martin, 2000). Similarly, MDP is capable of stimulating NF-κB-dependent gene transcription and pro-inflammatory cytokine production (Windheim et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Expression of macrophage CD14 receptor in the course of experimental inflammatory responses induced by lipopolysaccharide and muramyl dipeptide

Sládek¹,

Rysanek²

2008

Vet. Med. - Czech

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AbstrACt:The aim of this study was to determine whether expression of CD14 on macrophages is regulated differently during initiation and resolution of the inflammatory response caused by CD14-dependent (lipopolysaccharide) and CD14-independent (muramyldipeptide) bacterial signals. In cell suspensions from the site of inflammation we observed two types of macrophages: non-vacuolized ( N MAC) and vacuolized ( V MAC) cells. N MAC (monocyte-like cells) were dominant during the early stage of the inflammatory response, whilst V MAC contained phagocytosed apoptotic neutrophils in various stages of digestion. These latter cells were dominant during resolution (particularly at the last time point of 168 h). Intramammary instillation of muramyldipeptide (MDP) and lipopolysaccharide (LPS) resulted in a significant increase in the total count of CD14+ N MAC after 24 h (muramyldipeptide P < 0.01 and lipopolysaccharide P < 0.05) compared to phosphate buffered saline (PBS). During resolution of the inflammatory response, a gradual decrease in the total count of CD14+ N MAC was observed. The difference compared with PBS was significant at 48 h and 72 h after instillation of both bacterial agents (muramyldipeptide: P < 0.05; lipopolysaccharide: P < 0.05). A lower total count of CD14+ V MAC was observed as an effect of MDP and LPS at 24 h after induction (P < 0.05), when compared to PBS. During resolution, the total count of CD14+ V MAC increased. Differences (P < 0.01) were observed at 72 h and 168 h after LPS compared to PBS. We therefore assume that the expression of CD14 on macrophages is not regulated differently during the inflammatory responses caused by CD14-dependent and CD14-independent bacterial signals. On the other hand, the stage of the inflammatory response to MDP and LPS played an important role in the regulation of CD14 expression on macrophages.

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Section: Discussionmentioning

confidence: 99%

Expression of macrophage CD14 receptor in the course of experimental inflammatory responses induced by lipopolysaccharide and muramyl dipeptide

Sládek¹,

Rysanek²

2008

Vet. Med. - Czech

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“…The concentration of LBP is assumed to be 10 -100 ng/ml in the undiluted alveolar fluid, corresponding to a serum concentration of ϳ0.1-1% (54). In patients suffering from acute lung injury, bronchoalveolar concentrations of LBP have been documented to rise by ϳ100-fold (55). A recent paper reports that mice deficient in the expression of LBP have an impaired response to lung infection with Gram-negative organisms but not to pneumonia induced by Gram-positive organisms, supporting that LBP is not necessary for a sensitive innate immune response to Gram-positive-bacteria in the lung (56).…”

Section: Discussionmentioning

confidence: 99%

Cell Activation of Human Macrophages by Lipoteichoic Acid Is Strongly Attenuated by Lipopolysaccharide-binding Protein

et al. 2006

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Lipoteichoic acid (LTA) represents immunostimulatory molecules expressed by Gram-positive bacteria. They activate the innate immune system via Toll-like receptors. We have investigated the role of serum proteins in activation of human macrophages by LTA from Staphylococcus aureus and found it to be strongly attenuated by serum. In contrast, the same cells showed a sensitive response to LTA and a significantly enhanced production of tumor necrosis factor ␣ under serum-free conditions. We show that LTA interacts with the serum protein lipopolysaccharide-binding protein (LBP) and inhibits the integration of LBP into phospholipid membranes, indicating the formation of complexes of LTA and soluble LBP. The addition of recombinant human LBP to serum-free medium inhibited the production of tumor necrosis factor ␣ and interleukins 6 and 8 after stimulation of human macrophages with LTA in a dose-dependent manner. Using anti-LBP antibodies, this inhibitory effect could be attributed to soluble LBP, whereas LBP in its recently described transmembrane configuration did not modulate cell activation. Also, using primary alveolar macrophages from rats, we show a sensitive cytokine response to LTA under serum-free culture conditions that was strongly attenuated in the presence of serum. In summary, our data suggest that innate immune recognition of LTA is organ-specific with negative regulation by LBP in serum-containing compartments and sensitive recognition in serum-free compartments like the lung.

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“…Binding of LPS to mCD14 is upregulated by LPS-binding protein (LBP), an acute phase protein released by the liver during inflammation [12]. In response to LPS/LBP complexes, monocytes/macrophages release a spectrum of cytokines, including TNF-a, IL-1, IL-6 and IL-8, that initiate host defense response [26]. However, overwhelming production of TNF-a is the main causation of multiple organ failure and death as seen in "septic shock" [40].…”

Section: Introductionmentioning

confidence: 99%

Recombinant bovine soluble CD14 reduces severity of experimental Escherichia coli mastitis in mice

Lee

Paape²,

Zhao

2003

Vet. Res.

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-Endotoxin, or lipopolysaccharide (LPS), is responsible for pathogenesis of infections induced by Gram-negative bacteria, such as E. coli. The cellular response to LPS is modulated by interactions among LPS, LPS-binding protein (LBP) and CD14. Accumulated evidence shows that the soluble form of CD14 (sCD14) competes with membrane-bound CD14 (mCD14) for LPS and plays a pivotal role in regulating bacterial infection and septic shock caused by Gram-negative bacteria. Recombinant bovine sCD14 (rbosCD14) was produced by transfected insect sf/9 cells and its biological function was evaluated in mice. Eighty-one 8-week old BALB/cj female mice were randomly assigned to two groups, and injected intraperitoneally with either LPS (8 mg/g of body weight, n = 41) or LPS plus rbosCD14 (6.8 mg/g of body weight, n = 40). Survival rate at 24 h after injection for mice injected with either LPS or LPS plus rbosCD14 was 30 and 72%, respectively (P < 0.01). At 48 h survival rate was 7 and 37%, respectively (P < 0.01). To investigate the protective effect of rbosCD14 on experimentally induced mastitis in mice, two abdominal contralateral mammary glands of 7 lactating BALB/cj mice were injected through the teat canal with 10-20 colony-forming units (CFU) of Escherichia coli. One gland simultaneously received rbosCD14 (6 mg) and the other saline. At 24 h after challenge, glands that received rbosCD14 had less swelling and hemorrhaging, significantly lower bacterial counts (P < 0.05) and lower concentrations of TNF-a (P < 0.05). Results indicate that rbosCD14 is biologically functional and reduces mortality in mice from endotoxin shock and severity of intramammary infection by E. coli. mastitis / CD14 / LPS / Escherichia coli / TNF-a

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Recognition of Bacterial Endotoxin in the Lungs

Cited by 111 publications

References 53 publications

Expression of macrophage CD14 receptor in the course of experimental inflammatory responses induced by lipopolysaccharide and muramyl dipeptide

Expression of macrophage CD14 receptor in the course of experimental inflammatory responses induced by lipopolysaccharide and muramyl dipeptide

Cell Activation of Human Macrophages by Lipoteichoic Acid Is Strongly Attenuated by Lipopolysaccharide-binding Protein

Recombinant bovine soluble CD14 reduces severity of experimental Escherichia coli mastitis in mice

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