Vitamin D Binding Protein (Gc-Globulin)*

Cooke, Nancy E.; Haddad, John G.

doi:10.1210/edrv-10-3-294

Cited by 244 publications

(139 citation statements)

References 128 publications

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“…Vitamin D binding protein (Gc-globulin) is the primary vitamin D carrier protein, binding 85-90% of total circulating 25(OH)D (26). It was reported that Gc-globulin was associated with the neutrophil chemotactic activity of C5a (27).…”

Section: Discussionmentioning

confidence: 99%

Age-Related Vitamin D Deficiency Is Associated with the Immune Response in Children with Community-Acquired Pneumonia

Huang

Yang

2017

J Nutr Sci Vitaminol

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SummaryTo investigate vitamin D status in children with community-acquired pneumonia (CAP) and explore the association between vitamin D deficiency and the immune response in CAP children, 77 children with CAP were retrospectively analyzed. The baseline characteristics of patients were obtained from medical records. Based on the blood samples collected during diagnosis of CAP, the routine blood examination results and proportions of lymphocyte subsets were assessed. There were 71.4% (55/77) of patients with vitamin D deficiency among CAP children. The serum 25(OH)D level significantly decreased with age. Patients with vitamin D deficiency had a significantly higher neutrophil percentage, but significantly lower lymphocyte percentage and count as well as proportion of CD19 positive lymphocytes (CD191). Spearman's rho test further confirmed these positive correlations and negative correlations. Moreover, significant associations of vitamin D deficiency with age and the above immune markers were also confirmed by univariate logistic regression analysis. However, only age entered the backward stepwise regression model in multivariate analysis. Vitamin D status in CAP children was negatively associated with age. Age-related vitamin D deficiency may affect the immune response in children with CAP.

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Section: Discussionmentioning

confidence: 99%

Age-Related Vitamin D Deficiency Is Associated with the Immune Response in Children with Community-Acquired Pneumonia

Huang

Yang

2017

J Nutr Sci Vitaminol

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“…1 Group-specific component (Gc) protein, also known as vitamin D-binding protein (DBP), acts as a scavenger protein by forming a complex with actin (complexed Gc) that is subsequently removed from the circulation by macrophages in the reticuloendothelial system. 2,3 The amount of complexed and free Gc (i.e., Gc protein not complexed with actin) protein present in the blood is related directly to the extent of hepatic necrosis. In patients with severe ALF, serum levels of free Gc protein are decreased, levels of complexed Gc protein are increased, and the ratio of complexed to total Gc, expressed as a percentage, is increased.…”

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confidence: 99%

Immunonephelometric quantification of group-specific component protein in patients with acute liver failure

Wians

1997

Liver Transplantation

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Serum levels of group-specific component (Gc) protein are useful in evaluating the likelihood of survival in patients with acute liver failure (ALF) who may be candidates for liver transplant surgery. Most methods for quantifying Gc protein concentration are either isotopic, manual, technically demanding, and/or time consuming to perform, and thus are not well suited for routine clinical use in a hospital setting. We modified and evaluated a recently described nonisotopic, fully automated, immunonephelometric method for quantifying serum Gc protein concentration and compared it to our previous immunoblotting method. In addition, we evaluated the effect of G-actin on the immunonephelometric measurement of Gc protein. Serum samples from 20 patients with ALF and from 20 age-and sexmatched clinic patients without liver disease were quantified by both immunoblotting and immunonephelometry. We assessed the intra-assay precision, correlation, and diagnostic accuracy of these methods in discriminating between individuals with no preexisting liver disease and those with ALF. Actin in 1.3-to 4-fold excess of Gc protein levels demonstrated minimal to no interference in the quantification of Gc protein by immunonephelometry. Immunonephelometry was more precise than immunoblotting. Gc protein values by immunonephelometry were similar to those obtained by immunoblotting, and the diagnostic accuracy of Gc protein concentration by immunonephelometry was similar to that observed by immunoblotting. Immunonephelometry provides a nonisotopic, fully automated, rapid, precise, accurate, and cost-effective method for quantifying serum levels of total Gc protein that is well suited for routine use in a hospital-based clinical laboratory.

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“…Therefore, the next question we addressed was does 1,25 (OH) 2 D 3 need to be bound to DBP to have an inhibitory effect. For these experiments we exploited the fact that 25(OH)D 3 binds to DBP with a 10-fold tighter affinity than does 1,25 (OH) 2 D 3 (Cooke and Haddad, 1989), and that the 25(OH)D 3 form of the vitamin does not alter the co-chemotactic activity of DBP (Figs. 1B & 2).…”

Section: Resultsmentioning

confidence: 99%

“…This phenomenon almost certainly has physiological significance since DBP appears to be ubiquitous in the body (Cooke and Haddad, 1989). It is found at high concentrations in blood (6-7 μM) and has been detected in several other fluids including cerebrospinal fluid, bronchoalveolar lining fluid, seminal fluid, saliva, synovial fluid and breast milk.…”

Section: Discussionmentioning

confidence: 98%

Selective inhibition of the C5a chemotactic cofactor function of the Vitamin D binding protein by 1,25(OH)2 Vitamin D3

Shah

DiMartino

Trujillo

et al. 2006

Molecular Immunology

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The vitamin D binding protein (DBP) is a multifunctional plasma protein that can significantly enhance the chemotactic response to complement fragment C5a. The chemotactic cofactor function of DBP requires cell surface binding in order to mediate this process. The goal of this study was to investigate the effect of ligating DBP with its two primary physiological ligands, vitamin D and Gactin, on both binding to neutrophils and the ability to enhance chemotaxis to C5a. There was no difference in neutrophil binding between of the holo (bound) forms versus the apo (unbound) form of radioiodinated DBP, indicating that the cell binding region of DBP likely is distinct from the vitamin D sterol and G-actin binding sites. Likewise, G-actin, 25(OH)D 3 , and G-actin plus 25(OH) D 3 bound to DBP did not alter its capacity to enhance chemotaxis toward C5a. However, the active form of vitamin D (1,25(OH) 2 D 3 ) completely eliminated the chemotactic cofactor function of DBP. Dose response curves demonstrated that as little as 1 pM 1,25(OH) 2 D 3 significantly inhibited chemotaxis enhancement. Moreover, at physiological concentrations 1,25(OH) 2 D 3 needs to be bound to DBP to mediate the inhibitory effect. Neutrophil chemotaxis to optimal concentrations of C5a, formyl peptide, CXCL8 or leukotriene B 4 was not altered by 1,25(OH) 2 D 3 indicating that the active vitamin does not have a global inhibitory effect on neutrophil chemotaxis. Finally, inhibition of cell surface alkaline phosphatase with sodium orthovanadate completely reversed the inhibitory effect of 1,25(OH) 2 D 3 . These results indicate that the cell binding and co-chemotactic functions of DBP are not altered when the protein binds G-actin and/or vitamin D. Furthermore, the co-chemotactic signal from DBP can be eliminated or counteracted by 1,25(OH) 2 D 3 .

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Vitamin D Binding Protein (Gc-Globulin)*

Cited by 244 publications

References 128 publications

Age-Related Vitamin D Deficiency Is Associated with the Immune Response in Children with Community-Acquired Pneumonia

Age-Related Vitamin D Deficiency Is Associated with the Immune Response in Children with Community-Acquired Pneumonia

Immunonephelometric quantification of group-specific component protein in patients with acute liver failure

Selective inhibition of the C5a chemotactic cofactor function of the Vitamin D binding protein by 1,25(OH)2 Vitamin D3

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