Pantetheinase activity of membrane‐bound Vanin‐1: lack of free cysteamine in tissues of Vanin‐1 deficient mice

Pitari, Giuseppina; Malergue, Fabrice; Martin, Florent; Philippe, Jean‐Marc; Massucci, Maria; Chabret, Claude; Maras, Bruno; Duprè, Silvestro; Naquet, Philippe; Galland, Franck

doi:10.1016/s0014-5793(00)02110-4

Cited by 196 publications

(198 citation statements)

References 34 publications

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“…Cysteamine promotes the production of chemokines that attract neutrophils and inhibits ␥-glutamylcysteine synthetase, which is needed to synthesize the natural reducing agent glutathione (69,70). This suggests that increased Vanin-1 is likely to exacerbate inflammation dependent on neutrophils and oxidation, which is consistent with the decreased inflammation observed in S. mansoni-infected, Vnn1-deficient mice (71).…”

Section: Discussionmentioning

confidence: 99%

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Khodoun

Lewis²,

Yang

et al. 2007

The Journal of Immunology

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IL-4 and IL-13 are each bound by soluble receptors (sRs) that block their activity. Both of these sRs (sIL-4Rα and sIL-13Rα2) are present in low nanogram per milliliter concentrations in the serum from unstimulated mice, but differences in affinity and half-life suggest differences in function. Serum IL-4/sIL-4Rα complexes rapidly dissociate, releasing active IL-4, whereas sIL-13Rα2 and IL-13 form a stable complex that has a considerably longer half-life than uncomplexed IL-13, sIL-13Rα2, IL-4, or sIL-4Rα. Approximately 25% of sIL-13Rα2 in serum is complexed to IL-13; this percentage and the absolute quantity of sIL-13Rα2 in serum increase considerably during a Th2 response. sIL-13Rα2 gene expression is up-regulated by both IL-4 and IL-13; the effect of IL-4 is totally IL-4Rα-dependent while the effect of IL-13 is partially IL-4Rα-independent. Inhalation of an IL-13/sIL-13Rα2 complex does not affect the expression of IL-13-inducible genes but increases the expression of two genes, Vnn1 and Pira-1, whose products activate APCs and promote neutrophilic inflammation. These observations suggest that sIL-4Rα predominantly sustains, increases, and diffuses the effects of IL-4, whereas sIL-13Rα2 limits the direct effects of IL-13 to the site of IL-13 production and forms a stable complex with IL-13 that may modify the quality and intensity of an allergic inflammatory response.

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Section: Discussionmentioning

confidence: 99%

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Khodoun

Lewis²,

Yang

et al. 2007

The Journal of Immunology

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“…Vanin-1 genotyping was done by PCR. 26 The ank/ank/Vnn1 Ϫ/Ϫ mice were generated by crossing Ank/ank and Vnn1 Ϫ/Ϫ mice to generate double heterozygotes which were bred to generate Ank/Ank/ Vnn1 ϩ/ϩ , Ank/Ank/Vnn1 Ϫ/Ϫ , ank/ank/Vnn1 ϩ/ϩ , and ank/ ank/Vnn1 Ϫ/Ϫ littermates.…”

Section: Mice Studiedmentioning

confidence: 99%

“…9,22,23,25 Pantetheinases specifically hydrolyze pantetheine to pantothenic acid (vitamin B 5 ) and the cell-permeant sulfhydryl cysteamine (NH 2 -CH 2 -CH 2 -SH). 26,27 Cysteamine directly inhibits ␥-glutamylcysteine synthetase, the rate-limiting enzyme in synthesis of GSH. 22,23 Vnn1 Ϫ/Ϫ mice, which have a grossly normal phenotype, lack free cysteamine in tissues and demonstrate elevated stores of GSH in multiple tissues.…”

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confidence: 99%

Vanin-1 Pantetheinase Drives Increased Chondrogenic Potential of Mesenchymal Precursors in ank/ank Mice

Johnson

Yao

Lane

et al. 2008

The American Journal of Pathology

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Widespread endochondral and intramembranous ectopic bone formation is mediated by extracellular PP i deficiency that develops in ank/ank mice. Herein we report on the rapid condensation into chondrogenic nodules of cultured ank/ank bone marrow stromal cells (BMSCs). We compared the roles of increased chondrogenic potential versus altered osteoblast function in the ank/ank phenotype. To do so, we crossbred ank/ank mice with mice lacking Vanin-1 pantetheinase, which inhibits synthesis of the chondrogenesis regulator glutathione, since we observed increased Vanin-1 expression and pantetheinase activity and decreased glutathione in ank/ank BMSCs.

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“…Vanin-1-deficient mice develop normally but their tissues lack cysteamine and exhibit a modified stress response in part due to enhanced intracellular gluthatione levels [11,14]. Indeed, cysteamine inhibits c-glutamylcysteine synthetase, the ratelimiting enzyme of gluthatione synthesis [15,16].…”

Section: Introductionmentioning

confidence: 99%

Vanin‐1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

Meghari¹,

Berruyer-Pouyet²,

Lépidi³

et al. 2006

Eur J Immunol

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Q fever is caused by Coxiella burnetii, a bacterium that survives in MU. Vanin-1 is a membrane-anchored pantetheinase that controls tissue inflammation. Consequently, Vanin-1-deficient mice represent a unique mouse model in which stress-induced inflammation is limited by the reaction of resident tissue cells. To investigate the contribution of host tissues in the control of a bacterial infection, we infected Vanin-1-deficient mice with C. burnetii. Mortality and morbidity of mice were not affected. The lack of Vanin-1 had no effect on C. burnetii clearance but decreased the formation of granulomas in spleen and liver. Granuloma formation depends upon MU recruitment and activation in these tissues. Whereas the former was slightly impaired in mutant mice, the lack of Vanin-1 significantly affected the activation pattern of BM-derived MU stimulated by C. burnetii. While their microbicidal activity against C. burnetii was moderately impaired, they exhibited decreased inducible nitric oxide synthase (iNOS) and MCP-1 gene expression, and increased IL-10 and arginase expression. In liver from mutant mice, increased arginase expression and decreased expression of MCP-1 and iNOS were reminiscent of MU data. These results suggest a role of Vanin-1 in granuloma formation in response to C. burnetii by skewing MU activation toward an M2 program. See accompanying commentary http://dx

show abstract

Pantetheinase activity of membrane‐bound Vanin‐1: lack of free cysteamine in tissues of Vanin‐1 deficient mice

Cited by 196 publications

References 34 publications

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Vanin-1 Pantetheinase Drives Increased Chondrogenic Potential of Mesenchymal Precursors in ank/ank Mice

Vanin‐1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

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