Endotoxin-neutralizing capacity of soluble CD14

Schütt, Christine; Schilling, Tom; Grunwald, Uwe; Schönfeld, W.; Krüger, Christian

doi:10.1016/0923-2494(92)80082-v

Cited by 124 publications

(87 citation statements)

References 10 publications

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“…sCD14 can participate in cell activation indirectly by promoting transfer of LPS to membrane-bound CD14 (11) or directly by transferring LPS to Toll-like receptor 4/MD-2 complex on cells that do not express membrane-bound CD14 (12). The level of sCD14 increases in response to an LPS challenge (13).…”

Section: Introductionmentioning

confidence: 99%

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD

Poesen

Ramezani

Claes

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD.Design, setting, participants, & measurements We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR,60 ml/min per 1.73 m 2 for $3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006.Results Plasma sCD14 was negatively associated with eGFR (r=-0.34, P,0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P,0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (r=-0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up.Conclusions Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.

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Section: Introductionmentioning

confidence: 99%

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD

Poesen

Ramezani

Claes

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…sCD14 has two main functions. First, it can facilitate LPS transfer to lipoproteins, preventing over stimulation of the inflammatory response [20,35]. Alternatively, it can facilitate LPS binding to cells that do not express CD14 such as endothelial and epithelial cells, and cause activation of TLR-4 and release of cytokines [9].…”

Section: Introductionmentioning

confidence: 99%

Shedding of sCD14 by bovine neutrophils following activation with bacterial lipopolysaccharide results in down-regulation of IL-8

et al. 2007

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-CD14, the leukocyte co-receptor for lipopolysaccharide (LPS), is important in the response of bovine polymorphonuclear neutrophil leukocytes (PMN) to Gram-negative bacteria. In other species, the expression of CD14 on the surface of PMN was shown to increase after exposure to inflammatory stimuli. These newly expressed molecules may originate from either an intracellular pool or through new gene expression. We sought to characterize bovine PMN cell surface expression and shedding of CD14 molecules, and CD14's effect on secretion of the chemoattractants IL-8 and IL-1β by PMN. Bovine PMN were incubated in RPMI for 20 h at 37 • C with LPS (1, 10, 100 µg/mL). IL-8 release increased with treatment of 1 µg/mL LPS, but decreased 41.5 and 95% at the 10 and 100 µg/mL concentrations of LPS, respectively. In contrast, shedding of CD14 from the surface of PMN only increased at the highest concentration of LPS (100 µg/mL). Secretion of IL-1β was similar regardless of the LPS concentration used to stimulate PMN. The effect of PMN concentration (1 × 10 7 , 2.5 × 10 7 , 5 × 10 7 , and 10 × 10 7 /mL) on CD14 cell surface expression and shedding of IL-8 and IL-1β were also determined. Shedding of CD14 by PMN increased with increasing concentration of PMN after exposure to 0.1 and 10 µg/mL of LPS, while secretion of IL-8 decreased. IL-1β increased at the highest concentration of PMN. The use of real time polymerase chain reaction showed that CD14 mRNA expression was not different between control and LPS-stimulated cells, indicating that the sCD14 came from either membrane bound CD14 or a preformed pool. Our results demonstrate that release of CD14 from PMN suppresses secretion of IL-8, and may be an important regulatory mechanism for controlling excessive migration of PMN into the bovine mammary gland.CD14 / IL-8 / LPS / neutrophil / bovine

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“…The physiologic role of sCD 14 is unknown. It could act as a scavenger by neutralizing circulating LPS [13] shown that complexes ofsCD 14 with LPS activate these cells [14,15].We measured sequential serum concentrations of sCD 14 in 54 patients with gram-negative septic shock, compared these with levels in normal controls, and correlated sCD 14 levels with patient outcome. We also determined the biochemical form of serum sCD 14 by Western blotting and compared it with sCD 14 derived from normal monocytes.…”

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confidence: 99%

“…The physiologic role of sCD 14 is unknown. It could act as a scavenger by neutralizing circulating LPS [13] or, alternatively, it may playa harmful role by transmitting LPS effects on endothelial cells, which do not express membrane CD 14 [I4]. Indeed, it was recently shown that complexes ofsCD 14 with LPS activate these cells [14,15].…”

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confidence: 99%

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Increased Circulating Soluble Cd14 Is Associated With High Mortality In Gram-Negative Septic Shock

Landmann

Zimmerli²,

Sansano³

et al. 1995

Journal of Infectious Diseases

193

124

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The soluble glycoprotein sCD 14 binds lipopolysaccharide, a complex that activates endothelial cells and that may be crucial in gram-negative sepsis, Therefore, serum sCD14 was analyzed in 54 patients with gram-negative septic shock and in 26 healthy controls, sCD14 was tested by ELISA and Western blotting, Patients had higher sCD14 concentrations than controls (median, 3.23 vs. 2.48 #!g/mL, P = .002). Increased levels were associated with high mortality (median, 4.2 #Lg/mL in nonsurvivors vs. 2.8 #!g/mL in survivors, P = .001). sCD14 was found in two isoforms (49 and 55 kDa) in monocyte cultures. In sera only one of either form was detectable. Controls had the 49-kDa form, and patients had either the 49-or 55-kDa form, but patients with high levels of sCD14 had only the 55-kDa form. Twenty-one (53%) of 39 with the 55-kDa form and 8 (57%) of 14 with the 49-kDa form died. Thus, the level of sCD14 but not its biochemical form had a prognostic value in patients with gram-negative septic shock.Lipopolysaccharide (LPS) plays a key role in the pathophysiology of sepsis [I]. The LPS receptor on myeloid cells is the phosphatidylinositol-Iinked membrane glycoprotein CD 14 [2]. CD 14 occurs in a membrane-associated form and as a soluble (s) molecule [3,4]. sCD 14 is derived from the monocytic cell line Mono-Mac 6 in two forms [5]: A 48-kDa form is shed from the membrane of monocytes and MonoMac 6 cells [6,7], and a 56-kDa form is detectable in metabolically labeled Mono-Mac 6 cells and in sCD 14 purified from urine [3,5]. The serum concentration of sCD 14 is ,...., I millionfold higher than that ofcytokines [8]. Although much is known about cytokine liberation during experimental endotoxemia or sepsis, little is known about sCD 14 in these conditions [9][10][11][12]. Because CD 14 is the principle LPS receptor, the serum concentration ofsCD 14 may be modified during endotoxemia or sepsis. The physiologic role of sCD 14 is unknown. It could act as a scavenger by neutralizing circulating LPS [13] shown that complexes ofsCD 14 with LPS activate these cells [14,15].We measured sequential serum concentrations of sCD 14 in 54 patients with gram-negative septic shock, compared these with levels in normal controls, and correlated sCD 14 levels with patient outcome. We also determined the biochemical form of serum sCD 14 by Western blotting and compared it with sCD 14 derived from normal monocytes. MethodsPatients. The study population comprised 54 patients (33 males, 21 females) with documented gram-negative septic shock. Their median age was 58 years (range, 7-78). All were part of a previously described study that compared the efficacy of J5 hyperimmunoglobulin (n = 22) with standard intravenously (iv) administered IgG (n = 32) (Sandoglobulin; Sandoz Pharmaceuticals, Basel, Switzerland) [16]. The etiology ofseptic shock was established by the isolation of gram-negative bacteria from blood in 37 patients (69%). Of these, 30 had monomicrobial and 7 had polymicrobial bacteremia. Seventeen patients (3 t %) had documented gram-nega...

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Endotoxin-neutralizing capacity of soluble CD14

Cited by 124 publications

References 10 publications

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD

Shedding of sCD14 by bovine neutrophils following activation with bacterial lipopolysaccharide results in down-regulation of IL-8

Increased Circulating Soluble Cd14 Is Associated With High Mortality In Gram-Negative Septic Shock

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