Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages.

Wright, Samuel D.; Tobias, Peter S.; Ulevitch, Richard J.; Ramos, Robert

doi:10.1084/jem.170.4.1231

Cited by 309 publications

(177 citation statements)

References 15 publications

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“…Other studies have examined particles consisting of titanium alloy [2], titanium oxide [lo], cobalt-chrome [ll], polyethylene [3,11], and polymethylmethacrylate [3 I] and have included wear partiAdherent endotoxin may mediate these effects by increasing phagocytosis of the wear particles. Consistent 20 (2002) 696-703 697 with this possibility, adherent LPS can enhance phagocytosis of red blood cells [37,41]. In this study, we therefore examined the effect of adherent endotoxin on phagocytosis of titanium particles.…”

Section: Introductionmentioning

confidence: 83%

Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis

Collier

Goldberg

et al. 2002

Journal Orthopaedic Research

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Aseptic loosening of orthopaedic implants is thought to be primarily due to stimulation of cytokine production by wear particles from the implants. The cytokines increase osteoclast differentiation, leading to osteolysis and implant loosening. Accumulating evidence indicates that adherent endotoxin mediates the biological responses induced by the wear particles. One mechanism by which adherent endotoxin may act is by increasing phagocytosis of the wear particles. To test this hypothesis, the effect of adherent endotoxin on phagocytosis of titanium particles was determined. First, we developed reliable confocal and fluorescence microscopy methods to examine both the attachment and internalization steps of phagocytosis. Use of these methods showed that adherent endotoxin does not detectably alter the rate or the extent of phagocytosis of titanium particles by RAW 264.7 cells. Despite this lack of an effect on phagocytosis, adherent endotoxin dramatically increases the ability of RAW 264.7 cells to produce TNF-a and induce osteoclast differentiation. Thus, adherent endotoxin mediates these biological responses by a mechanism that does not rely on increased phagocytosis. These results also demonstrate that phagocytosis is not sufficient to induce cytokine production and osteoclast differentiation but do not rule out the possibility that phagocytosis is required for induction of these responses by titanium particles with adherent endotoxin.

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Section: Introductionmentioning

confidence: 83%

Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis

Collier

Goldberg

et al. 2002

Journal Orthopaedic Research

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“…31) and the LBP/lipid A interaction (data not shown). LBP catalyzes the transfer of endotoxin from the solubilized to the membranebound form; i.e., it promotes the binding of endotoxin to the endotoxin receptor CD14 on macrophages, and this process is thought to represent the starting point of the shock cascade (1,3,42). In view of the ability of the peptides to block this interaction, we anticipated that they inhibit TNF-␣ secretion by endotoxinstimulated macrophages.…”

Section: Discussionmentioning

confidence: 99%

Synthetic Endotoxin-Binding Peptides Block Endotoxin- Triggered TNF-α Production by Macrophages In Vitro and In Vivo and Prevent Endotoxin-Mediated Toxic Shock

Dankesreiter

Hoess

Schneider‐Mergener

et al. 2000

The Journal of Immunology

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Lipid A, the conserved portion of endotoxin, is the major mediator of septic shock; therefore, endotoxin-neutralizing molecules could have important clinical applications. Here we show that peptides derived from Limulus anti-LPS factor (LALF), bactericidal/permeability increasing protein (BPI) and endotoxin-binding protein, bind to lipid A and block the recombinant LALF/lipid A interaction in vitro. Because their neutralizing capacity in vitro as well as in vivo has been limited, we created hybrid peptides comprising two endotoxin-binding domains. The hybrid molecule LL-10-H-14, containing endotoxin-binding domains from LALF and endotoxin-binding protein, turned out to be the most active peptide within the series of peptides tested here to inhibit the CD14/lipid A interaction and is able in vitro to block the endotoxin-induced TNF-α release of murine macrophages up to 90%. Furthermore, LL-10-H-14 not only reduced peak serum levels of TNF-α of mice when preinjected but also reduced TNF-α levels when given 15 min after the endotoxin challenge. As compared with other peptides, only LL-10-H-14 is able to strongly decrease endotoxin-stimulated TNF-α release by human macrophage cell lines as well as by PBMC. Furthermore, the hybrid peptide is protective against endotoxin-provoked lethal shock. As such, LL-10-H-14 could have prophylactic and/or therapeutic properties in humans for the management of septic shock.

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“…For LPS recognition, three additional proteins are required, including LPS binding protein (161), CD14 (160), and MD-2 (135). TLR4 signals via the two distinct pathways, MyD88-dependent and Trif-dependent pathways (112).…”

Section: Tlr-signaling Pathwaysmentioning

confidence: 99%

Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart

Chao¹

2009

American Journal of Physiology-Heart and Circulatory Physiology

212

166

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Toll-like receptors (TLRs) represent the first line of host defense against microbial infection and play a pivotal role in both innate and adaptive immunity. TLRs recognize invading pathogens through molecular pattern recognition, transduce signals via distinct intracellular pathways involving a unique set of adaptor proteins and kinases, and ultimately lead to the activation of transcription factors and inflammatory responses. Among 10 TLRs identified in humans, at least two exist in the heart, i.e., TLR2 and TLR4. In addition to the critical role of these in mediating cardiac dysfunction in septic conditions, emerging evidence suggests that the TLRs can also recognize endogenous ligands and may play an important role in modulating cardiomyocyte survival and in ischemic myocardial injury. In animal models of ischemia-reperfusion injury or in hypoxic cardiomyocytes in vitro, the administration of a sublethal dose of lipopolysaccharide, which signals through TLR4, reduces subsequent myocardial infarction, improves cardiac functions, and attenuates cardiomyocyte apoptosis. By contrast, a systemic deficiency of TLR2, TLR4, or myeloid differentiation primary-response gene 88, an adaptor critical for all TLR signaling, except TLR3, leads to an attenuated myocardial inflammation, a smaller infarction size, a better preserved ventricular function, and a reduced ventricular remodeling after ischemic injury. These loss-of-function studies suggest that both TLRs contribute to myocardial inflammation and ischemic injury in the heart although the exact contribution of cardiac (vs. circulatory cell) TLRs remains to be defined. These recent studies demonstrate an emerging role for TLRs as a critical modulator in both cell survival and tissue injury in the heart.

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Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages.

Cited by 309 publications

References 15 publications

Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis

Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis

Synthetic Endotoxin-Binding Peptides Block Endotoxin- Triggered TNF-α Production by Macrophages In Vitro and In Vivo and Prevent Endotoxin-Mediated Toxic Shock

Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart

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