Inhibition of Endotoxin-Induced Cytokine Release and Neutrophil Activation in Humans by Use of Recombinant Bactericidal/Permeability-Increasing Protein

Möhlen, M. A. M. Von Der; Kimmings, A. N.; Wedel, Nancy; Mevissen, M. L. C. M.; Jansen, J.; Friedmann, Nadav; Lorenz, Todd J.; Nelson, Betty J.; White, Mark L.; Bauer, Robert J.; Hack, C. E.; Eerenberg, A. J. M.; Deventer, S. J. H. Van

doi:10.1093/infdis/172.1.144

Cited by 119 publications

(60 citation statements)

References 45 publications

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“…during treatment of the infection with antibiotics (18). Thus, intact BPI or a recombinant N-terminal fragment attenuates LPSinduced neutrophil and endothelial cell activation in vitro (20,21), as well as secretion of inflammatory mediators, neutrophil activation and circulatory changes in vivo (18,22,23). BPI, or BPI analogs, may therefore be beneficial as adjunctive treatment of severe infections (24,25).…”

Section: Discussionmentioning

confidence: 99%

Bactericidal/permeability‐increasing protein inhibits endotoxin‐induced vascular nitric oxide synthesis

Ciornei

Egesten

Engström

et al. 2002

Acta Anaesthesiol Scand

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Background: Endotoxin (lipopolysaccharide, LPS) up‐regulates inducible nitric oxide synthase (iNOS) in blood vessels during septic shock. This promotes the production of nitric oxide (NO), leading to dilation of the vessels. The aim of the study was to investigate the effects of the LPS‐binding endogenous antibiotic bactericidal/permeability‐increasing protein (BPI) on the action of LPS on the blood vessels wall and to identify possible influence on underlying NO‐related mechanisms.Methods: Isolated segments of rat thoracic aorta and cultured primary smooth muscle cells were incubated for 5–48 h in the presence of the following combinations of compounds: (a) LPS; (b) interleukin‐1β (IL‐1β); (c) BPI; (d) BPI + LPS; (e) BPI + IL‐1β or (f) neither BPI, LPS nor IL‐1β (control). After incubation of intact segments, we measured smooth muscle contraction in response to phenylephrine and accumulation of the NO end products nitrate and nitrite in surrounding medium. Western blot was used to assess the levels of inducible nitric oxide synthase (iNOS) in cultured cells.Results: Both LPS and IL‐1β decreased contractility and increased NO production, as well as iNOS. Co‐incubation with BPI attenuated all the effects of LPS but only the effects of prolonged exposure to IL‐1β in cultured cells.Conclusion: We conclude that BPI attenuates the LPS‐induced changes in vascular reactivity by inhibiting the expression of iNOS resulting in decreased NO formation and restored responsiveness to vasoconstrictors. The data suggest that BPI can prevent circulatory disturbances during Gram‐negative sepsis.

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Section: Discussionmentioning

confidence: 99%

Bactericidal/permeability‐increasing protein inhibits endotoxin‐induced vascular nitric oxide synthesis

Ciornei

Egesten

Engström

et al. 2002

Acta Anaesthesiol Scand

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“…This property of BPI has prompted preclinical and subsequent clinical testing of recombinant amino-terminal fragments of BPI. Phase I trials in healthy human volunteers and multiple clinical trials have now well proven that BPI is neither toxic nor immunogenic in normal individuals or in seriously ill patients (Von Der Mohlen et al, 1995). Trials of BPI administration have been or are being performed in various pathologic conditions including severe pediatric meningococcemia, hemorrhagic trauma, peritoneal infections, and cystic fibrosis (Elsbach, 1998).…”

Section: Granule Proteinsmentioning

confidence: 99%

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Witko‐Sarsat

Rieu

Descamps‐Latscha

et al. 2000

Laboratory Investigation

945

723

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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. However, these studies strongly suggested that BPI could act in vivo and help resolve GNB infection and endotoxin-induced inflammation.…”

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%

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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Inhibition of Endotoxin-Induced Cytokine Release and Neutrophil Activation in Humans by Use of Recombinant Bactericidal/Permeability-Increasing Protein

Cited by 119 publications

References 45 publications

Bactericidal/permeability‐increasing protein inhibits endotoxin‐induced vascular nitric oxide synthesis

Bactericidal/permeability‐increasing protein inhibits endotoxin‐induced vascular nitric oxide synthesis

Neutrophils: Molecules, Functions and Pathophysiological Aspects

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

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