Bactericidal/Permeability-Increasing Protein Release in Whole Blood Ex Vivo: Strong Induction by Lipopolysaccharide and Tumor Necrosis Factor- 

Abstract

In this study, the release of bactericidal/permeability-increasing protein (BPI), which is stored in polymorphonuclear leukocytes (PMNL), was analyzed in a whole blood ex vivo system. Of the microbial products tested, lipopolysaccharide (LPS) most potently induced BPI release; FMLP, serum-treated zymosan (STZ), and lipoteichoic acid (LTA) also induced BPI release. In addition, the inflammatory mediator tumor necrosis factor (TNF)-alpha potently activated PMNL in whole blood, via TNF receptor p55, to release BPI, whereas interleukin (IL)-1, IL-8, platelet activating factor, and C5a were poor inducers of BPI release. STZ and phorbol myristate acetate, but not LPS, FMLP, or LTA, stimulated isolated PMNL to release BPI. BPI was released in comparable magnitude with the azurophilic granule protein elastase. Furthermore, both proteins were released with similar kinetics, which started within 30 min after onset of stimulation and lasted 1-4 h.

Priming of cytokine release and increased levels of bactericidal permeability-increasing protein in the blood of animal facility workers

“…At present we observe a slight down-regulation of LPS-binding protein in animal workers exposed to low amounts of LPS; thus, less LPS can be bound to CD14 molecules (Wright et al 1990). The clear increase in BPI observed in animal workers suggests an antagonistic up-regulation for binding of LPS and could be caused by increased TNF release acting on PMN TNF-receptor R55 (Dentener et al 1997). The up-regulation of the soluble TNF-receptor R75 observed in the animal workers usually correlates with high levels of TNF production.…”

Genetic variation in bactericidal/permeability-increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation

“…While LBP catalyzes transfer of lipopolysaccharide monomers to CD14 to promote TLR4-dependent cell activation and release of inflammatory mediators, BPI antagonizes the action of LBP by binding the lipid A region of lipopolysaccharide to facilitate aggregation of lipopolysaccharide, thus inhibiting transfer of lipopolysaccharide to CD14. [49][50][51][52] BPI is also capable of inhibiting bacterial growth, activating bacterial phospholipid hydrolysis, and penetrating the inner bacterial membrane to dissipate electrochemical gradients required for bacterial viability. 53,54 The neutrophil has been considered the primary source of BPI.…”

Cloning and Characterization of the Homolog of Mammalian Lipopolysaccharide-Binding Protein and Bactericidal Permeability-Increasing Protein in Rainbow TroutOncorhynchus mykiss

“…into rainbow trout (33)(34)(35). Head kidneys and/or livers were collected from rainbow trout before and after LPS treatment.…”