The Primary Role of Lymphoreticnlar Cells in the Mediation of Host Responses to Bacterial Endotoxim

Michalek, Suzanne M.; Moore, Robert N.; McGhee, Jerry R.; Rosenstreich, David L.; Mergenhagen, Stephan E.

doi:10.1093/infdis/141.1.55

Cited by 198 publications

(72 citation statements)

References 39 publications

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“…This was further illustrated in a mouse strain unresponsive to LPS: C3H/HeJ mice. When bone marrow from LPS-responsive C3H/HeN mice was injected into irradiated C3H/HeJ recipients, they became responsive to LPS (363). In addition, C3H/ HeJ mice could be rendered sensitive to LPS after injection of macrophages from C3H/HeN mice (147).…”

Section: Cellular Defensementioning

confidence: 99%

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

2003

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Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory cytokines and adhesion molecules is discussed in detail. In addition, the roles of a number of other receptors that bind bacterial compounds such as scavenger receptors and their modulating role in inflammation are described. Finally, the therapies for the treatment of bacterial sepsis and septic shock are discussed in relation to the action of the aforementioned receptors and proteins

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Section: Cellular Defensementioning

confidence: 99%

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

2003

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“…LPS-activated cells can induce microcirculatory dysfunction and inflammatory changes, resulting in various types of tissue damage, circulatory failure, and occasionally death. [48][49][50] To prevent excessive and prolonged responses of host innate immune cells to LPS, the host may acquire a system for downregulation to ensure safe responses to LPS and/or unresponsiveness to a second stimulation with LPS, a process known as LPS tolerance. 51 Several previous studies have demonstrated LPS tolerance in THP-1 cells.…”

Section: Mbl Interacting With Tlr4 Regulates Lps Signalingmentioning

confidence: 99%

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

et al. 2011

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Mannan-binding lectin (MBL) plays a key role in the lectin pathway of complement activation and can influence cytokine expression. Toll-like receptor 4 (TLR4) is expressed extensively and has been demonstrated to be involved in lipopolysaccharide (LPS)-induced signaling. We first sought to determine whether MBL exposure could modulate LPS-induced inflammatory cytokine secretion and nuclear factor-kB (NF-kB) activity by using the monocytoid cell line THP-1. We then investigated the possible mechanisms underlying any observed regulatory effect. Using ELISA and reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we found that at both the protein and mRNA levels, treatment with MBL suppresses LPS-induced tumor-necrosis factor (TNF)-a and IL-12 production in THP-1 cells. An electrophoretic mobility shift assay and western blot analysis revealed that MBL treatment can inhibit LPS-induced NF-kB DNA binding and translocation in THP-1 cells. While the binding of MBL to THP-1 cells was evident at physiological calcium concentrations, this binding occurred optimally in response to supraphysiological calcium concentrations. This binding can be partly inhibited by treatment with either a soluble form of recombinant TLR4 extracellular domain or anti-TLR4 monoclonal antibody (HTA125). Activation of THP-1 cells by LPS treatment resulted in increased MBL binding. We also observed that MBL could directly bind to the extracellular domain of TLR4 in a dose-dependent manner, and this interaction could attenuate the binding of LPS to cell surfaces. Taken together, these data suggest that MBL may affect cytokine expression through modulation of LPS-/TLR-signaling pathways. These findings suggest that MBL may play an important role in both immune regulation and the signaling pathways involved in cytokine networks.

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“…The key role for TLR4 in vivo was illustrated when the C3H/HeJ strain of mice, long known to be resistant to LPS-induced mortality, was found to be homozygous for a naturally occurring single base pair mutation in the TLR4 gene, leading to a complete absence of functional protein (9). When bone marrow-derived cells from these mice were transferred to irradiated wild-type control mice, relative protection against LPS-induced mortality resulted, implying that leukocyte TLR4 signaling is necessary to cause the systemic effects of LPS (10).…”

mentioning

confidence: 99%

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Cunningham

Wang

Guo

et al. 2004

The Journal of Immunology

223

186

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Toll-like receptor 4 (TLR4) is present on monocytes and other cell types, and mediates inflammatory events such as the release of TNF after exposure to LPS. C3H/HeJ mice are resistant to LPS-induced mortality, due to a naturally occurring mutation in TLR4. We therefore hypothesized that LPS-induced acute renal failure (ARF) requires systemic TNF release triggered by LPS acting on extrarenal TLR4. We injected C3H/HeJ mice and C3H/HeOuJ controls with 0.25 mg of LPS, and sacrificed them 6 h later for analysis of blood urea nitrogen (BUN) and kidney tissue (n = 8 per group). In contrast to C3H/HeOuJ controls, C3H/HeJ mice were completely resistant to LPS-induced ARF (6-h BUN of 32.3 ± 1.1 vs 61.7 ± 5.6 mg/dl). C3H/HeJ mice released no TNF into the circulation at 2 h (0.00 vs 1.24 ± 0.16 ng/ml), had less renal neutrophil infiltration (6.4 ± 1.0 vs 11.4 ± 1.3 neutrophils per high power field), and less renal apoptosis, as assessed by DNA laddering. Transplant studies showed that C3H/HeJ recipients of wild-type kidneys (n = 9) were protected from LPS-induced ARF, while wild-type recipients of C3H/HeJ kidneys (n = 11) developed severe LPS-induced ARF (24-h BUN 44.0 ± 4.1 vs 112.1 ± 20.0 mg/dl). These experiments support our hypothesis that LPS acts on extrarenal TLR4, thereby leading to systemic TNF release and subsequent ARF. Renal neutrophil infiltration and renal cell apoptosis are potential mechanisms by which endotoxemia leads to functional ARF.

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The Primary Role of Lymphoreticnlar Cells in the Mediation of Host Responses to Bacterial Endotoxim

Cited by 198 publications

References 39 publications

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

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