Structural relationship between the soluble and membrane-bound forms of human monocyte surface glycoprotein CD 14

Bažil, V; Baudyš, Miroslav; Hilgert, I; Stefanová, I; Low, Martin G.; Zbrožek, J.; Hořejšı́, Václav

doi:10.1016/0161-5890(89)90048-5

Cited by 145 publications

(106 citation statements)

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“…17, 20]. After release, sCDl4 circulates in the bloodstream [8]. Whereas the serum concentration of sCD 14 is constant in normal persons (see Methods), we found increased levels in patients with gram-negative septic shock.…”

Section: Labeling With [35s] Methionine Monocytes Were Incubatedmentioning

confidence: 50%

“…The monocytic cell line Mono-Mac 6 releases two sCDl4 forms [5], and in sCDl4 purified from urine two forms are identified under reducing conditions [3,8]. However, the expression of two CD 14 isoforms has not been seen in normal monocytes, which are the major source of serum sCD 14.…”

Section: Labeling With [35s] Methionine Monocytes Were Incubatedmentioning

confidence: 99%

“…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].…”

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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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Section: Labeling With [35s] Methionine Monocytes Were Incubatedmentioning

confidence: 50%

Section: Labeling With [35s] Methionine Monocytes Were Incubatedmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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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“…Two forms patient's urine. By exposing peripheral blood monocytes to diÂerent mycobacterial fractions, we hope to determine of sCD14 were identified in serum and also have been shown to be produced by activated monocytes [24,25].…”

Section: Discussion Resultsmentioning

confidence: 99%

Soluble urinary CD14 after intravesical bacille Calmette‐Guérin immunotherapy for carcinoma in situ

Jackson

Lien²,

Alexandroff

et al. 1997

British Journal of Urology

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Objective To characterize the production of the monoalthough in most patients there was a minor band of reactivity at 54 kDa. A panel of human bladder cancer cyte activation marker, soluble CD14 (sCD14), after bacille Calmette-Guérin (BCG) immunotherapy for cell lines did not react with the anti-CD14 monoclonal antibodies 3C10, 5C5 and BA8, and the antibodies superficial bladder cancer. Patients and methods Nineteen patients with carcinoma also failed to react with malignant epithelial cells in frozen sections of untreated bladder tumour. in situ were treated with a standard regimen of intravesical BCG. Urine samples were collected after each Furthermore, sCD14 was not secreted by cultured bladder tumour cells. The source of urinary sCD14 is instillation and analysed; the levels of soluble CD14 were determined by an enzyme-linked immunosorbent likely to be the resident and infiltrating macrophages in the bladder wall. Freshly isolated peripheral blood assay, the molecular weight confirmed by Western blotting and the possible cell source investigated using monocytes secreted sCD14 in response to BCG in a manner analogous to stimulation with bacterial lipoimmunohistochemistry.Results The mean levels of sCD14 were higher in polysaccharide. Conclusion A soluble form of CD14 is secreted into the patients with persistent carcinoma (designated as failures) than in those who had successful complete urine of patients who receive intravesical BCG. The measurement of soluble urinary CD14 could be of responses (responders) to BCG immunotherapy. The diÂerences were statistically significant, with P= prognostic significance for the response to immunotherapy. 0.034 at instillation 4 and P=0.027 at instillation 5 for the total mass of sCD14, and P=0.049 at instilKeywords Bacille Calmette-Guérin, BCG, lipopolysaccharide, bladder cancer, CD14 lation 4 for the concentration of sCD14. The predominant type of sCD14 in urine was the 48 kDa form, bladder wall is infiltrated by many neutrophils, lympho-

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“…Soluble CD14 (sCD14), a coreceptor for bacterial lipopolysaccharide, is a proinflammatory cytokine that may be more directly connected to bone health. In humans, it is produced by both hepatocytes [13] and proteolytic cleavage of membrane-bound CD14 [14] on monocytes and macrophages, which are precursors to mature osteoclasts [15][16][17]. sCD14 acts as an acute phase reactant [18] and regulates Tlymphocyte activation and function [19] with decreases in interleukin -4 (IL-4) and interferon gamma production.…”

Section: Introductionmentioning

confidence: 99%

Soluble CD14 and fracture risk

et al. 2015

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Summary Soluble CD14 (sCD14) is an inflammatory marker associated with osteoclasts. Using Cox proportional hazards models, we found a positive association between plasma levels of sCD14 and risk of incident fracture among participants in the Cardiovascular Health Study. sCD14 may be useful in identifying those at risk for fracture. Introduction Soluble CD14, a proinflammatory cytokine, is primarily derived from macrophages/monocytes that can differentiate into osteoclasts. The purpose of this study was to examine the relationship between sCD14 levels and osteoporotic fractures. Methods In the Cardiovascular Health Study, 5462 men and women had sCD14 levels measured at baseline. Incident hip fractures (median follow-up time 12.5 years) and incident composite fractures (defined as the first hip, pelvis, humerus, or distal radius fracture, median follow-up 8.6 years) were identified from hospital discharge summaries and/or Medicare claims data. Cox proportional hazards models were used to model the association between sCD14 levels and time to incident hip or composite fracture, overall and as a function of race and gender.Results In unadjusted models, there was a positive association between sCD14 levels (per 1 standard deviation increase, i.e., 361.6 ng/mL) and incident hip (HR, 1.26; 95 % CI, 1.17, 1.36) and composite (HR, 1.20; 95 % CI, 1.12, 1.28) fractures. When models were fully adjusted for demographics, lifestyle factors, and medication use, these associations were no longer significant. However, in whites, the association of sCD14 levels with hip fractures remained significant in fully adjusted models (HR, 1.11; 95 % CI, 1.01-1.23). Associations of sCD14 levels with hip and composite fracture did not differ between men and women. Conclusions In this large cohort of community-dwelling older adults, higher sCD14 levels were associated with an increased risk of incident hip fractures in whites.

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Structural relationship between the soluble and membrane-bound forms of human monocyte surface glycoprotein CD 14

Cited by 145 publications

References 12 publications

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

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

Soluble urinary CD14 after intravesical bacille Calmette‐Guérin immunotherapy for carcinoma in situ

Soluble CD14 and fracture risk

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