Changes in Polymorphonuclear Leukocyte Surface and Plasma Bactericidal/Permeability-Increasing Protein and Plasma Lipopolysaccharide Binding Protein During Endotoxemia or Sepsis

Calvano, Steve E.; Thompson, W. A.; Marra, Marian N.; Coyle, Susette M.; Riesthal, Herbert F. de; Trousdale, Rhonda K.; Barie, Philip S.; Scott, Randy W.; Moldawer, Lyle L.; Lowry, Stephen F.

doi:10.1001/archsurg.1994.01420260116016

Cited by 70 publications

(46 citation statements)

References 41 publications

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“…Therefore, concentrations of 100 ng/ml were used in a series of initial studies examining the in vitro function of LBP, all demonstrating LPS-enhancing activities of LBP. However, humans exhibit higher constitutive levels of LBP of 5-15 g/ml (21)(22)(23). Furthermore, we have shown by promoter analysis studies that the LBP gene is transcriptionally activated during the acute phase response (24), and acute phase serum levels of LBP during sepsis, consistent with these studies, are clearly elevated reaching peak levels of up to 200 g/ml (23).…”

Section: Introductionsupporting

confidence: 85%

LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.

Lamping¹,

Dettmer²,

Schröder³

et al. 1998

J. Clin. Invest.

321

245

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Section: Introductionsupporting

confidence: 85%

LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.

Lamping¹,

Dettmer²,

Schröder³

et al. 1998

J. Clin. Invest.

321

245

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“…In experimental endotoxemia, plasma BPI levels rose both at early (Ͻ2 h) and later (Ͼ5 h) times after administration of LPS and did not appear to fit the acute-phase response pattern (34). Furthermore, in septic adult patients, median plasma BPI levels either did (7,34) or did not (35) differ from those of controls. The laboratory diagnosis of infection in newborn infants is difficult.…”

Section: Discussionmentioning

confidence: 84%

Extracellular Release of Bactericidal/Permeability-Increasing Protein in Newborn Infants

Nupponen

2002

Pediatric Research

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Upon activation, polymorphonuclear leucocytes (PMN) release bactericidal/permability-increasing protein, (BPI) from their azurophil granules. BPI selectively binds to the lipopolysaccharide (LPS) on gram-negative bacteria and induces their death. This study examined plasma BPI concentration levels in healthy newborns and in newborns with clinical sepsis, and the ability of PMN from preterm and term infants to release BPI. We also studied the release of myeloperoxidase (MPO), and the surface expression of adhesion molecule CD11b on PMN. In infants with clinical sepsis, plasma BPI concentration was higher, 27.8 g/L [8.6 -883; median (range)] (n ϭ 11), than in healthy term infants 8.9 g/L (3.9 -179) (n ϭ 17), and in adults 7.3 g/L (0.7 -18.4) (n ϭ 15); p ϭ 0.014, Kruskal-Wallis. In preterm infants (n ϭ 8), the ability of PMN to release BPI in vitro after stimulation with PMA was 8.8, in term infants it was 15.9 (n ϭ 29; p Ͼ 0.05 vs. preterm infants) and in adults 23.4 ng/10 6 PMN (n ϭ 15; p ϭ 0.024 and p Ͼ 0.05 vs. preterm and term infants, respectively Newborn infants, especially those born prematurely, are at risk for overwhelming bacterial infections. A number of immaturities in the host defense system have been reported in newborn infants. Among the immune mechanisms that apparently function suboptimally are the PMN (1). PMN contain multiple antibiotic proteins such as BPI, which is found in human PMN and eosinophils. BPI selectively binds to the LPS on the outer membrane of Gramnegative bacteria, causing immediate growth arrest followed by irreversible damage and then the death of the bacterium (2). BPI also blocks the endotoxic effects of LPS and promotes phagocytosis of BPI-coated bacteria (3, 4).BPI has been localized to azurophil granules, where its hydrophobic C-terminal end is believed to anchor it to the granule membrane. Studies of PMN conducted in vitro suggest that BPI is capable of acting against Gram-negative bacteria in the intracellular environment. Data on isolated cells stimulated to secrete granule contents in vitro and on plasma derived from animals and humans with sepsis in vivo have demonstrated that a portion of cellular BPI stores is released from stimulated PMN (5-9

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“…Acute-phase levels of LBP in human sera are strongly elevated, reaching concentrations of up to 200 g/ml, which is 20-fold higher than normal levels (4,10,11). The function of these elevated LBP levels has been associated with an inhibitory effect on LPSinduced cell activation and was thought to be a host mechanism to blunt an otherwise overwhelming immune reaction (25,38,46).…”

Section: Discussionmentioning

confidence: 99%

Acute-Phase Concentrations of Lipopolysaccharide (LPS)-Binding Protein Inhibit Innate Immune Cell Activation by Different LPS Chemotypes via Different Mechanisms

et al. 2005

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The chain length of bacterial lipopolysaccharide (LPS) is a crucial factor for host-pathogen interaction during bacterial infection. While rough (R)-type and smooth (S)-typeLipopolysaccharide (LPS) is a prominent cell wall component of gram-negative bacteria and represents one of the most potent activators of the human innate immune system (36). A high sensitivity of the host for detecting LPS is mandatory in order to mount an early and rapid response against invading gram-negative bacteria. Research of the last decade has revealed the chemical composition and the requirements for biologic activity of LPS (2). While a certain set of lipid chains within the lipid A anchor and specific carbohydrates of the core region are absolutely required for activity, the long O chain consisting of up to 80 repeating oligosaccharide units varies greatly between different bacterial strains (35). Numerous reports have shown that the chain length of the carbohydrate unit of LPS that results in either a long (smooth [S]-type) or a short (rough [R]-type) O chain influences the host-pathogen interaction. Studies comparing R-and S-type LPS of Salmonella isolates have shown that colonization of the gut differs (30), as does resistance to complement-mediated killing (20). In addition, interaction with host neutrophils differs in bacteria carrying either R-or S-form LPS (31), which may be due to a distinct sensitivity to the activity of bactericidal/permeabilityincreasing protein (BPI), a neutrophilic bactericidal protein of the host (5).Monocytes and macrophages are important regulatory and effector cells in innate immunity, and they express a specific receptor system for the detection of LPS represented by the combined actions of the membrane-bound isoform of CD14 (mCD14) with the central transmembrane signaling unit of Toll-like receptor 4 (TLR-4) and the accessory protein MD-2 (1, 29). Lower concentrations of LPS-binding protein (LBP), a protein closely related to BPI, have been documented to enhance the sensitivity for LPS by 3 to 4 orders of magnitude by catalyzing the binding of LPS to CD14 (14,37), thus facilitating the release of numerous mediators, among them cytokines such as tumor necrosis factor alpha, interleukin-1␤, and interleukin-6 (34, 36).Whereas early LPS recognition is crucial for the host to mount an immune reaction against invading gram-negative bacteria, regulatory mechanisms are important to prevent an overwhelming reaction that may lead to the development of pathological conditions and dysregulation of the immune system, as observed in sepsis and septic shock. Several mechanisms to blunt an immune reaction initiated by LPS have been described, including the induction of cellular and systemic states of LPS tolerance (24,41,45), cellular internalization and subsequent endolysosomal deacylation of major endotoxic forms of LPS (28), and the neutralizing transfer of LPS to plasma lipoproteins such as high-density lipoprotein (HDL) followed by intestinal excretion via the liver-bile duct pathway (27). Moreover, sever...

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Changes in Polymorphonuclear Leukocyte Surface and Plasma Bactericidal/Permeability-Increasing Protein and Plasma Lipopolysaccharide Binding Protein During Endotoxemia or Sepsis

Cited by 70 publications

References 41 publications

LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.

LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.

Extracellular Release of Bactericidal/Permeability-Increasing Protein in Newborn Infants

Acute-Phase Concentrations of Lipopolysaccharide (LPS)-Binding Protein Inhibit Innate Immune Cell Activation by Different LPS Chemotypes via Different Mechanisms

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