A recombinant amino terminal fragment of bactericidal/permeability-increasing protein inhibits the induction of leukocyte responses by LPS

Mészáros, Károly; Parent, J B; Gazzano-Santoro, Hélène; Little, R.; Horwitz, Arnold H.; Parsons, Thomas F.; Theofan, Georgia; Grinna, Lynn S.; Weickmann, Joachim L.; Elsbach, Peter

doi:10.1002/jlb.54.6.558

Cited by 56 publications

(35 citation statements)

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“…BPI attenuates LPS-mediated endothelial damage and IL-6 production as well as LPS-mediated NO, TNF-␣, IL-1, IL-6, and IL-8 production by macrophages and whole blood (11,67,91,362,584). In vivo, BPI or rBPI 23 reduced LPS-or bacterium-induced TNF-␣ release, liver damage, NO production, and mortality and protected against cardiovascular depression (7,117,275,321).…”

Section: Lipopolysaccharide-and Lipoteichoic Acid-binding Proteins Nementioning

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: Lipopolysaccharide-and Lipoteichoic Acid-binding Proteins Nementioning

confidence: 99%

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

2003

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“…Because low concentrations of BPI can inhibit LBP-promoted LPS signaling (23)(24)(25), we investigated whether low (substoichiometric) concentrations of BPI can block the enhancing effects of LBP on the fluorescence of FITC-LPS. To this end, the fluorescence of FITC-LPS was monitored both after preincubation for 30 min with increasing amounts of BPI to permit formation of LPS-BPI complexes and after subsequent addition of LBP.…”

Section: Comparison Of Effects Of Lbp and Bpi On Fitc-lps-mentioning

confidence: 99%

Lipopolysaccharide (LPS)-binding Proteins BPI and LBP Form Different Types of Complexes with LPS

Tobias

Soldau

Iovine

et al. 1997

Journal of Biological Chemistry

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119

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Lipopolysaccharide (LPS)-binding protein (LBP) andbactericidal/permeability-increasing protein (BPI) are closely related LPS-binding proteins whose binding to LPS has markedly different functional consequences. To gain better insight into the possible basis of these functional differences, the physical properties of LBP-LPS and BPI-LPS complexes have been compared in this study by sedimentation, light scattering, and fluorescence analyses. These studies reveal dramatic differences in the physical properties of LPS complexed to LBP versus BPI. They suggest that of the two proteins, only LBP can disperse LPS aggegates. However, BPI can enhance both the sedimentation velocity and apparent size of LPS aggregates while inhibiting LPS-LBP binding even at very low (1:40 to 1:20) BPI:LPS molar ratios.The lipopolysaccharide (LPS)-binding protein 1 (LBP) and the bactericidal/permeability-increasing protein (BPI) are both LPS-interactive mammalian proteins with approximately 45% amino acid sequence identity (1, 2). LPS is considered to be the principal component of Gram-negative bacteria that alerts the host to invading bacteria and triggers defensive responses (3, 4). These responses are usually beneficial and effective but may also become excessive and lead to endotoxic shock (3-5). Both LBP and BPI modulate the bioactivity of LPS (2,3,5). LBP is a plasma protein that catalyzes the transfer of LPS from LPS aggregates to other LPS-binding proteins (3, 6 -9). Prominent among these is CD14, a surface molecule of myeloid cells that is also present in the circulation as a soluble protein. LBP and CD14 together represent the main pathway by which cells recognize low concentrations of LPS and are stimulated to respond to 10,11). In contrast to the LPS-stimulatory properties of LBP, binding of LPS by BPI results in inhibition of the bioactivities of LPS (2). BPI is produced by polymorphonuclear leukocytes and stored in its azurophilic granules (12, 13). It contributes substantially to both the intracellular and extracellular antibacterial activity of polymorphonuclear leukocyte-rich inflammatory exudates toward Gram-negative bacteria (14, 15). The high affinity of BPI for LPS accounts for the target-cell specificity of the antibiotic activity of BPI for Gram-negative bacteria (2, 16). In contrast to BPI, binding of LBP to bacterial envelope LPS does not produce detectable membrane alterations or other antibacterial effects.We have recently described the use of fluorescein-labeled LPS (FITC-LPS) as well as metabolically labeled ([ 3 H]LPS) and sucrose density gradients to characterize the formation and physical properties of complexes of LPS with LBP and the soluble form of CD14 (7). In this report we describe results obtained by studying the binding of FITC-LPS and [ 3 H]LPS to BPI using the techniques described earlier and in addition compare the effects of LBP and BPI on the light scattering properties of LPS. The results obtained reveal striking differences in the physical properties of LBP-LPS and BPI-LPS complexes. Thus, un...

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“…BPI is specifically cytotoxic for Gram-negative bacteria, attributable to its strong attraction to the lipopolysaccharide (LPS) in the outer membrane of the Gram-negative bacterial envelope [15]. In addition to blocking bacterial proliferation, BPI also inhibits LPS-mediated release of tumour necrosis factor and other cytokines [16,17]. It thus serves as an important natural host defence against Gram-negative bacteria, but not against Gram-positive bacteria.…”

Section: Discussionmentioning

confidence: 99%

Comparative microbicidal activity of synovial fluid on arthritogenic organisms

Inman

Chiu

1996

Clinical and Experimental Immunology

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SUMMARYThere is strong circumstantial evidence to support the concept that local microbial antigens play a key role in the synovitis of reactive arthritis (ReA) patients. It is not at all clear whether these antigens reflect the sequelae of previously viable organisms once resident in the joint. To address the microbicidal activity of synovial fluid (SF) we performed quantitative cultures of arthritogenic organisms (Salmonella typhimurium, Shigella flexneri, Klebsiella pneumoniae) and controls (Escherichia coli, Staphylococcus aureus) in the presence of SF from patients with ReA. There was a dramatic inhibitory effect of SF on the Gram-negative organisms (mean 1 . 35

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A recombinant amino terminal fragment of bactericidal/permeability-increasing protein inhibits the induction of leukocyte responses by LPS

Cited by 56 publications

References 0 publications

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

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

Lipopolysaccharide (LPS)-binding Proteins BPI and LBP Form Different Types of Complexes with LPS

Comparative microbicidal activity of synovial fluid on arthritogenic organisms

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