Protective Effects of a Recombinant N-Terminal Fragment of Bactericidal/Permeability Increasing Protein on Endotoxic Shock in Conscious Rabbits

Yang, Lin; Ws, Ammons; Wj, Leach; Ah, Kung

doi:10.1097/00024382-199411000-00005

Cited by 19 publications

(11 citation statements)

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“…In brief summary, in a variety of animal models, recombinant human BPI (rBPI) and its amino-terminal derivate (rBPI 21 ), were protective against lethal and sub-lethal challenges with Gram-negative bacteria and endotoxin [11,[58][59][60][61]. Subsequent studies in humans, including in meningococcal sepsis, also showed a significant protective effect of BPI [12][13][14][15][61][62][63][64], although not yet sufficient to lead to an approved clinical application.…”

Section: Bpi Actions During Host: Gnb Interactionsmentioning

confidence: 99%

“…BPI-endotoxin interactions initiate the cytotoxic effects of BPI toward GNB and also lead to potent neutralization of endotoxin activity [10]. These properties have suggested that BPI could play an important role in arrest of GNB infection and resolution of endotoxin-driven inflammation and have stimulated pre-clinical and clinical studies of the possible protective actions of recombinant BPI in settings in which endogenous mechanisms controlling GNB infection and endotoxin-induced inflammation seem inadequate [11][12][13][14][15]. Studies of BPI have also led to the recognition of a variety of clinical settings in which auto-antibodies to BPI are manifest [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

Schultz

Weiss

2007

Clinica Chimica Acta

111

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Gram-negative bacteria (GNB) and their endotoxin present a constant environmental challenge. Endotoxins can potently signal mobilization of host defenses against invading GNB but also potentially induce severe pathophysiology, necessitating controlled initiation and resolution of endotoxin-induced inflammation to maintain host integrity. The bactericidal/permeability-increasing protein (BPI) is a pluripotent protein expressed, in humans, mainly neutrophils. BPI exhibits strong anti-microbial activity against GNB and potent endotoxin-neutralizing activity. BPI mobilized with neutrophils in response to invading GNB can promote intracellular and extracellular bacterial killing, endotoxin neutralization and clearance, and delivery of GNB outer membrane antigens to dendritic cells. Tissue expression by dermal fibroblasts and epithelia could further amplify local levels of BPI and local interaction with GNB and endotoxin, helping to constrain local tissue infection and inflammation and prevent systemic infection and systemic inflammation. This review article focuses on the structural and functional properties of BPI with respect to its contribution to host defense during GNB infections and endotoxin-induced inflammation and the genesis of auto-antibodies against BPI that can blunt BPI activity and potentially contribute to chronic inflammatory disease.

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Section: Bpi Actions During Host: Gnb Interactionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

Schultz

Weiss

2007

Clinica Chimica Acta

111

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“…A peptide named rBPI 21 of which sequence was derived from the residues 1-191 of the BPIP, was produced and its efficacy was assessed on the protection of animal suffering from endotoxemia. Treatment of laboratory animals with the rBPI 21 resulted in reduction of the severity of tissue injuries and mortality [14][15][16].…”

Section: Bactericidal/permeability-increasing Protein (Bpip)mentioning

confidence: 99%

Endotoxin-Neutralizing Peptides as Gram-Negative Sepsis Therapeutics

Wong

Luk²

2009

PPL

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Bacterial endotoxin [e.g. lipopolysaccharide (LPS)] can trigger systemic hyper-inflammatory that subsequently leads to multiple organ failure and lethality (gram-negative sepsis). This paper describes the development of endotoxin-neutralizing peptides that potentially treat sepsis. These peptides have been derived from bactericidal/permeability-increasing protein (BPIP), anti-microbial peptides, and leukocyte CD18 antigen and some of these peptides have been tested in clinical studies.

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“…Furthermore, this study showed that rBPI 23 treatment resulted in a preservation of respiratory functions. 41 Further proof of the beneficial effects of rBPI 23 on respiratory function in endotoxic states comes from studies with experimental lung injury and pneumonia caused by gram-negative organisms. In a porcine model of endotoxemic adult respiratory distress syndrome, rBPI 23 administration significantly reduced endotoxin-induced hypoxemia and alveolitis.…”

Section: Animal Studiesmentioning

confidence: 99%

Potential applications of N-terminal recombinant fragments of bactericidal/permeability-increasing protein in liver surgery

et al. 1999

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Bactericidal/permeability-increasing protein (BPI) was first isolated by Elsbach and Weiss in 1978. 1,2 It is a natural host-defense protein of 55 kd found in the azurophilic granules of human neutrophils, which are important in the host defense against infections. The protein was named after one of its first discovered properties, the potential to kill bacteria by increasing the permeability of their cell walls. 1,2 This ability to kill bacteria has led to further studies of the functions of BPI, from which researchers have discovered several potentially useful properties. In this article, we first give a brief review of the most important in vitro and in vivo studies showing the functions and properties of BPI and then focus on the potential applications of one of the more stable recombinant BPIs, rBPI 21 , in the field of liver surgery and transplantation. The Main Effects of BPI Antibacterial ActionBPI shows antimicrobial activity against a wide range of gram-negative bacteria. 1-3 The cell envelope of gram-negative bacteria consists of the cytoplasmic membrane, peptidoglycan layer, and an additional barrier, the outer membrane, which is strictly asymmetric with respect to its lipid composition. The outer leaflet of this membrane is composed mainly of lipopolysaccharides (LPS; endotoxins). LPS consists of an oligosaccharide or polysaccharide and a covalently linked glycolipid component (lipid A) that anchors the LPS in the outer membrane. 4 The selectivity of BPI against gram-negative bacteria has been attributed to the strong attraction of BPI for this LPS in the bacterial envelope, especially the high affinity for its lipid A component. 5,6 It has become evident that the LPS structure primarily determines bacterial sensitivity. Strains bearing LPS with short polysaccharide chains in their outer membrane are the most sensitive. Long polysaccharide chains sterically hinder the access of BPI to the binding sites in the inner core and the lipid A regions of LPS, thereby reducing the affinity of BPI for the envelope LPS, necessitating higher ambient BPI concentrations to achieve the required amount of bound BPI to produce its biological effects. 3,6,7 The cytotoxic effect of BPI on gram-negative bacteria can be divided into two stages. When BPI binds to the outer membrane, several immediate effects are manifest, including arrest of bacterial growth, discrete changes in the permeability of the outer membrane, and selective activation of several envelope enzymes, which degrade phospholipids and peptidoglycans. These changes are evident despite preservation of the functional integrity of the biochemical machinery in the nongrowing bacteria. In fact, certain manipulations result in repair of the envelope alterations and resumption of growth, therefore indicating that the initial effects of BPI are not directly bactericidal. 2,8 However, when this process is continued, alterations of the cytoplasmic membrane are produced, resulting in an impairment of the energy metabolism that leads to an irreversible growth arre...

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Protective Effects of a Recombinant N-Terminal Fragment of Bactericidal/Permeability Increasing Protein on Endotoxic Shock in Conscious Rabbits

Cited by 19 publications

References 0 publications

The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

Endotoxin-Neutralizing Peptides as Gram-Negative Sepsis Therapeutics

Potential applications of N-terminal recombinant fragments of bactericidal/permeability-increasing protein in liver surgery

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