Separation and purification of a potent bactericidal/permeability-increasing protein and a closely associated phospholipase A2 from rabbit polymorphonuclear leukocytes. Observations on their relationship.

Elsbach, Peter; Weiss, Jerrold; Franson, Richard C.; Beckerdite-Quagliata, S; Schneider, Achim; Harris, Lesley K.

doi:10.1016/s0021-9258(19)86622-x

Cited by 225 publications

(30 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An important agent in the antimicrobial apparatus of PMNs toward gram-negative bacteria such as E. coli is a cationic, membrane-active, bactericidal protein that has been isolated in our laboratory from rabbit and human PMNs (4,19). The bactericidal activity of crude extracts of rabbit and human PMNs, and of intact leukocytes as well, toward several non-encapsulated [K1(-)] strains of E. coli and Salmonella typhimurium seems to be primarily due to the action of these bactericidal/permeability-increasing proteins (BPIs) (21).…”

mentioning

confidence: 99%

Sensitivity of K1-Encapsulated Escherichia coli to Killing by the Bactericidal/Permeability-Increasing Protein of Rabbit and Human Neutrophils

et al. 1982

View full text Add to dashboard Cite

The presence of K1 capsular polysaccharides increases the resistance of Escherichia coli to killing by serum and phagocytosis by polymorphonuclear leukocytes (PMNs). To determine whether K1 capsule impedes the action of intracellular bactericidal systems of PMNs, we compared the sensitivity of several K1-encapsulated and non-encapsulated strains of E. coli to killing by the bactericidal/permeability-increasing protein (BPI) isolated from rabbit and human PMNs. BPI appears to be the principal bactericidal agent of PMNs toward E. coli and other gram-negative bacteria (Weiss et al., J. Clin. Invest. 69 :959-970, 1982). The presence of K1 capsule was monitored by sensitivity to K1-specific bacteriophages. The non-encapsulated strains used represent both random bacteremic isolates and non-encapsulated derivatives of K1-encapsulated strains obtained by selection for resistance to K1-specific phages. We found little or no difference in the sensitivity of K1-encapsulated and non-encapsulated E. coli to killing by neutralized acid extracts of rabbit PMNs. Bacterial killing by these crude fractions can be attributed to the action of BPI because: (i) bacterial killing was blocked by immune (anti-BPI) immunoglobulin but not by preimmune immunoglobulin and (ii) comparison of the dose-response curves of bacterial killing by crude extracts and by purified BPI showed that the bactericidal activity of crude fractions corresponded closely to the BPI content. Human and rabbit BPIs exhibited similar bactericidal potency toward K1-encapsulated E. coli ; i.e., <5 μg of either protein killed >90% of 2.5 × 10 7 bacteria. Thus, the potent bactericidal action of BPI toward E. coli is not impeded by K1 capsule, suggesting that the virulence of K1-encapsulated E. coli is a consequence of extracellular survival but not of resistance to intracellular killing.

show abstract

mentioning

confidence: 99%

Sensitivity of K1-Encapsulated Escherichia coli to Killing by the Bactericidal/Permeability-Increasing Protein of Rabbit and Human Neutrophils

et al. 1982

View full text Add to dashboard Cite

show abstract

“…A variety of cationic polypeptides purified from the granules of rabbit, human, and bovine neutrophils have been reported to exert antimicrobial or antiviral activity in vitro (3,5,6,8,18,19,21,25,26). They differ in size, spectrum of activity, and efficiency.…”

Section: Discussionmentioning

confidence: 99%

Small, antibacterial and large, inactive peptides of neutrophil granules share immunoreactivity to a monoclonal antibody

et al. 1988

View full text Add to dashboard Cite

Monoclonal antibodies were raised against a bactericidal protein fraction that was purified from an extract of bovine neutrophil granules and that was previously shown (A. Savoini, R. Marzari, L. Dolzani, D. Serranò, G. Graziosi, R. Gennaro, and D. Romeo, Antimicrob. Agents Chemother. 26:405-407, 1984) to inhibit bacterial DNA synthesis. One of these antibodies, BP97, was covalently linked to Affi-Gel 10 and was used for immunoaffinity chromatography of granule extracts. Elution of the bound proteins, followed by reversed-phase high-performance liquid chromatography, generated several peptides whose molecular weights fell in the range of 1,600 to 64,000 and which reacted to BP97 but not to other mouse monoclonal or polyclonal antibodies. The reaction to BP97 appeared to be specific, inasmuch as a full panel of cationic oligo- or polypeptides was not recognized by this monoclonal antibody. Among the purified granule polypeptides, the more cationic ones (with molecular weights of 4,300 to 8,000) inhibited the growth of Escherichia coli at a MIC of 12 to 50 micrograms/ml. In addition, a 1,600-molecular-weight, highly cationic peptide also inhibited the growth of Staphylococcus aureus and Staphylococcus epidermidis at MICs of 3 to 8 micrograms/ml.

show abstract

“…Moreover, BPI was shown to enhance the immune response (elevated levels of TNFα, IL-6 and IL-8) toward Gram-positive ligands in peripheral blood mononuclear cells (PBMCs) when synthetic bacterial lipopeptides, lipoteichoic acid (major cell wall component of Gram-positive bacteria), and lysates of Gram-positive bacteria were used [ 32 ]. Interestingly, BPI was not shown to have a direct bactericidal effect on Gram-positive bacteria in previous studies [ 12 , 41 ].…”

Section: Structural and Functional Characteristics Of Bpimentioning

confidence: 94%

Killing three birds with one BPI: Bactericidal, opsonic, and anti-inflammatory functions

Theprungsirikul

Skopelja-Gardner

Rigby

2021

Journal of Translational Autoimmunity

View full text Add to dashboard Cite

Bactericidal/permeability-increasing protein (BPI) is an anti-microbial protein predominantly expressed in azurophilic granules of neutrophils. BPI has been shown to mediate cytocidal and opsonic activity against Gram-negative bacteria, while also blunting inflammatory activity of lipopolysaccharide (LPS). Despite awareness of these functions in vitro, the magnitude of the contribution of BPI to innate immunity remains unclear, and the nature of the functional role of BPI in vivo has been submitted to limited investigation. Understanding this role takes on particular interest with the recognition that autoimmunity to BPI is tightly linked to a specific infectious trigger like Pseudomonas aeruginosa in chronic lung infection. This has led to the notion that anti-BPI autoantibodies compromise the activity of BPI in innate immunity against P. aeruginosa , which is primarily mediated by neutrophils. In this review, we explore the three main mechanisms in bactericidal, opsonic, and anti-inflammatory of BPI. We address the etiology and the effects of BPI autoreactivity on BPI function. We explore BPI polymorphism and its link to multiple diseases. We summarize BPI therapeutic potential in both animal models and human studies, as well as offer therapeutic approaches to designing a sustainable and promising BPI molecule.

show abstract

Separation and purification of a potent bactericidal/permeability-increasing protein and a closely associated phospholipase A2 from rabbit polymorphonuclear leukocytes. Observations on their relationship.

Cited by 225 publications

References 24 publications

Sensitivity of K1-Encapsulated Escherichia coli to Killing by the Bactericidal/Permeability-Increasing Protein of Rabbit and Human Neutrophils

Sensitivity of K1-Encapsulated Escherichia coli to Killing by the Bactericidal/Permeability-Increasing Protein of Rabbit and Human Neutrophils

Small, antibacterial and large, inactive peptides of neutrophil granules share immunoreactivity to a monoclonal antibody

Killing three birds with one BPI: Bactericidal, opsonic, and anti-inflammatory functions

Contact Info

Product

Resources

About