Soluble HLA-G is absent from human embryo cultures: A reassessment of sHLA-G detection methods

Sageshima, Noriko; Shobu, Takanori; Awai, Keiko; Hashimoto, Hiratsugu; Yamashita, Masanori; Takeda, Noriyo; Odawara, Yasushi; Nakanishi, Mari; Hatake, Kiyohiko; Ishitani, Akiko

doi:10.1016/j.jri.2007.02.010

Cited by 39 publications

(25 citation statements)

References 41 publications

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“…However, no biochemical evidence of its occurrence has been reported that might also shed light on the question of whether it is formed by shedding or by alternative gene splicing. Its detection has almost entirely been carried out by ELISA, and questions have been raised about the specificity of this immunological test (15,16). In addition, a Western blot was recently reported that showed immunoreactive material of the correct size for full-length HLA-G (Ϸ40 kDa) (17), mainly present in EVT with far smaller amounts at the basal plate and chorion.…”

Section: Discussionmentioning

confidence: 99%

“…However, the membranebound HLA-G homodimer, sometimes called G1, was recently shown to be the major form expressed by isolated EVT (14). It is unlikely that any of the other forms G2-G7 that have been postulated to result from alternative gene splicing occur as physiologically relevant proteins, with the possible exception of G5, soluble HLA-G (15)(16)(17). Recent observations from several groups (18)(19)(20)(21) suggest that at least one function of HLA-G could be to modulate cytokine secretion from decidual leukocytes to induce immune tolerance, control EVT invasion, and/or contribute to vascular remodeling of spiral arteries to allow for successful embryo implantation and pregnancy maintenance.…”

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confidence: 99%

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HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

Houser²,

Nicotra³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

177

150

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Human decidual CD14 ؉ macrophages and CD56 ؉ NK cells were isolated from material obtained after first-trimester pregnancy terminations. Each cell type expressed a specific surface receptor for histocompatibility leukocyte antigen (HLA)-G (an MHC class Ib protein that is expressed on extravillous trophoblasts), LILRB1 on CD14 ؉ macrophages and KIR2DL4 on CD56 ؉ NK cells. Cross-linking with anti-LILRB1 or anti-KIR2DL4 resulted in up-regulation of a small subset of mRNAs including those for IL-6, IL-8, and TNF␣ detected using a microarray representing 114 cytokines. Incubation with transfectants expressing the HLA-G homodimer (but not with transfectants expressing the HLA-G monomer) resulted in secretion of the same cytokine proteins from both leukocyte sets. Moreover, cytokine secretion from both leukocyte sets was blocked by both the appropriate anti-receptor mAb and by anti-HLA-G. The amount of these cytokines secreted by decidual macrophages was substantially greater than that secreted by decidual NK cells. VEGF was constitutively secreted by both cell types. LILRB1, which contains an immunoreceptor tyrosine-based switch motif, functions here as an activating receptor, although it has been known as an inhibitory receptor. KIR2DL4 also functions as an activating receptor, although it also has the potential to function as an inhibitory receptor. Secretion of proinflammatory and proangiogenic proteins supports a role for these leukocytes in important processes that are essential for successful pregnancy, but they may represent only a portion of the proteins that are secreted.IL-6 ͉ IL-8 ͉ pregnancy ͉ trophoblast ͉ VEGF

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

Houser²,

Nicotra³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

177

150

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“…Due to the low sHLA-G concentration in embryo cultures (EC), the HLA-G immunodetection method and sample treatment strongly determine the reliability of the sHLA-G measurement in embryo culture supernatants. Technical difficulties have led to very controversial results in the past [100,[104][105][106][107][108][109][110][111][112][113][114][115][116][117][118] but are being resolved. sHLA-G in embryo culture supernatants is mostly measured by sandwich ELISA or ALBIA (addressable laser bead immunoassay) techniques.…”

Section: Hla-g Expression In Preimplantation Embryos and Its Clinicalmentioning

confidence: 99%

The importance of HLA-G expression in embryos, trophoblast cells, and embryonic stem cells

Rizzo

Vercammen

Velde

et al. 2010

Cell. Mol. Life Sci.

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The nonclassical HLA-G molecule is a trophoblast-specific molecule present in almost every pregnancy. It differs from classical HLA class I molecules by the low degree of allelic variants and the high diversity of protein structures. HLA-G is reported to be a tolerogenic molecule that acts on cells of both innate and adaptive immunity. At the maternal-fetal interface HLA-G seems to be responsible largely for the reprogramming of local maternal immune response. This review will focus on the HLA-G gene expression profile in pregnancy, in preimplantation embryos, and in human embryonic stem cells with emphasis on the structural diversity of the HLA-G protein and its potential functional and diagnostic implications.

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“…During recent years, several studies suggested a relationship between the production of sHLA-G molecules by early embryos and an increased implantation rate in IVF protocols (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)12). Two studies (36,37) failed to detect sHLA-G molecules in embryo culture supernatants, probably due to technical discrepancies, as suggested by the recent review by Warner et al (38). It is important to develop a very high quality level in sHLA-G detection methodology to overcome these problems in order to evaluate the exact amount of sHLA-G produced by an in vitro cultured embryo (39) and to establish the functional role of sHLA-G during early embryo development (40).…”

Section: Discussionmentioning

confidence: 99%

Production of sHLA-G molecules by in vitro matured cumulus-oocyte complex

Rizzo

Canto²,

Stignani³

et al. 2009

Int J Mol Med

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Abstract. Oocyte selection with the highest competence is a major goal in IVF. Several studies demonstrated that nonclassical HLA class I HLA-G molecule modulation creates a tolerogenic microenvironment at the feto-maternal interface and is implicated in embryo implantation. This study investigated if soluble HLA-G molecules producted by the cumulus-oocyte complex (COC) are markers of oocyte maturation. sHLA-G molecule levels were analyzed using Bio-Plex assay in 152 COC supernatants obtained from 42 women and maturated by an 'in vitro maturation procedure'. The presence of sHLA-G molecules was confirmed by Western blotting technique. The results demonstrate detectable amounts of sHLA-G molecules ranging from 300 to 800 pg/ml in 14/73 (19%) COCs that generated mature oocytes and complete absence of detectable sHLA-G antigens in the supernatants of COCs that corresponded to immature oocytes. The detection of sHLA-G molecules in the COC culture supernatants corresponding to matured oocytes is proposed to be a marker to identify gametes with higher functionality. This non-invasive marker could be used, in addition to morphological approaches, to reduce the number of fertilized oocytes and transferred embryos.

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Soluble HLA-G is absent from human embryo cultures: A reassessment of sHLA-G detection methods

Cited by 39 publications

References 41 publications

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

The importance of HLA-G expression in embryos, trophoblast cells, and embryonic stem cells

Production of sHLA-G molecules by in vitro matured cumulus-oocyte complex

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