scholarly journals Elevated 1-αHydroxylase Activity in Monocytes from Patients with Active Tuberculosis

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Yi-Ching Tung ◽  
Tsan-Teng Ou ◽  
Wen-Chan Tsai
Keyword(s):  
Ex Vivo ◽  
Active Tuberculosis ◽  
Uremic Patient ◽  
Alternative Source ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Renal Tubular Cells ◽  
25 Hydroxyvitamin D ◽  
Renal Tubular ◽  
Alternative Sites

A uremic patient developed hypercalcemia after tuberculosis infection, and his ionized calcium levels correlated with 1,25-dihydroxyvitamin D3(1,25(OH)2D3) levels. We performed further studies to determine whether monocytes are alternative sites of 1,25(OH)2D3conversion beyond renal tubular cells. Using an ex vivo bioassay, in this study, we found that 1-αhydroxylase (CYP27B1) activity in monocytes is significantly higher in patients with active tuberculosis (TB) than in those with frequent TB contact. However, when monocytes from patients with active TB were restimulated with antigen derived fromMycobacterium tuberculosis, less 1,25(OH)2D3was observed. In contrast, the level of 1,25(OH)2D3was unchanged in those with frequent TB contact. We conclude that monocytes may be an alternative source of 1-αhydroxylase that could convert 25-hydroxyvitamin D3to the more active 1,25(OH)2D3.

scholarly journals Vitamin D upregulates the macrophage complement receptor immunoglobulin in innate immunity to microbial pathogens

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Annabelle G. Small ◽  
Sarah Harvey ◽  
Jaspreet Kaur ◽  
Trishni Putty ◽  
Alex Quach ◽  
...  
Keyword(s):  
Vitamin D ◽  
Innate Immunity ◽  
Surface Expression ◽  
Microbial Pathogens ◽  
Cell Surface Expression ◽  
Complement Receptor ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Multistep Process ◽  
25 Hydroxyvitamin D

AbstractVitamin D deficiency remains a global concern. This ‘sunshine’ vitamin is converted through a multistep process to active 1,25-dihydroxyvitamin D3 (1,25D), the final step of which can occur in macrophages. Here we demonstrate a role for vitamin D in innate immunity. The expression of the complement receptor immunoglobulin (CRIg), which plays an important role in innate immunity, is upregulated by 1,25D in human macrophages. Monocytes cultured in 1,25D differentiated into macrophages displaying increased CRIg mRNA, protein and cell surface expression but not in classical complement receptors, CR3 and CR4. This was associated with increases in phagocytosis of complement opsonised Staphylococcus aureus and Candida albicans. Treating macrophages with 1,25D for 24 h also increases CRIg expression. While treating macrophages with 25-hydroxyvitamin D3 does not increase CRIg expression, added together with the toll like receptor 2 agonist, triacylated lipopeptide, Pam3CSK4, which promotes the conversion of 25-hydroxyvitamin D3 to 1,25D, leads to an increase in CRIg expression and increases in CYP27B1 mRNA. These findings suggest that macrophages harbour a vitamin D-primed innate defence mechanism, involving CRIg.

scholarly journals Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

2016 ◽  
Vol 37 (5) ◽  
pp. 521-547 ◽  
Author(s):  
Peter J. Tebben ◽  
Ravinder J. Singh ◽  
Rajiv Kumar
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Active Form ◽  
Elevated Serum ◽  
Diagnosis And Treatment ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Stone Formers ◽  
25 Hydroxyvitamin D

AbstractHypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

An international comparison of vitamin D metabolite measurements.

1984 ◽  
Vol 30 (3) ◽  
pp. 399-403 ◽  
Author(s):  
M J Jongen ◽  
F C Van Ginkel ◽  
W J van der Vijgh ◽  
S Kuiper ◽  
J C Netelenbos ◽  
...  
Keyword(s):  
Reference Sample ◽  
Plasma Samples ◽  
Internal Reference ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Three Samples ◽  
25 Hydroxyvitamin D ◽  
Laboratory Survey ◽  
Standard Solutions

Abstract An international 19-laboratory survey was organized to compare assays for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D in plasma. Each participant received two ethanolic standard solutions of each metabolite and eight plasma samples. Each laboratory used its usual procedures. Mean interlaboratory coefficients of variation (CVs) for the eight plasma samples were 35%, 43%, and 52% for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D, respectively. Average CVs for the standard solutions were 27%, 23%, and 25%, respectively. Of the eight plasma samples, five had the same concentration for one of the metabolites. One sample was diluted to 0.6 times its original concentration and three samples were fortified with one or more of the metabolites under investigation. Fourteen of 18 laboratories (78%) could distinguish between the five unchanged samples and the modified ones with their 25-hydroxyvitamin D assay. Nine of 12 (75%) could distinguish the modified samples from the other samples with the 24,25-dihydroxyvitamin D assay. Only eight of 15 (53%) could do this their 1,25-dihydroxyvitamin D assay. Values from different laboratories evidently cannot be intercompared without making an actual comparison of the assay procedures. Furthermore, in case of clinical applications of these assays, each laboratory should establish its own reference values and should continually use an internal reference sample to assess the precision of the procedures.

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