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1.
Placenta ; 25(1): 1-8, 2004 Jan.
Article in English | MEDLINE | ID: mdl-15013633

ABSTRACT

The survival of the allogeneic conceptus has long been an immunological paradox. Medawar was the first to propose an evasive mechanism based on the concept of self/non-self recognition described in classical transplantation immunology. Since then, several newer models of self/non-self recognition have been proposed, such as the PAMP/PRR system, the Missing Self and the Danger Hypothesis. The present paper considers the fetal-maternal relationship in the context of all these models. The conclusion reached is that none of them is really appropriate because the interface between trophoblast cells of the fetal placenta and the leukocytes of the maternal decidua is unique. Pregnancy is not simply a case of acceptance or rejection like a transplant. The immunological mechanism must provide a balanced environment whereby the conceptus is nurtured by the mother and yet prevented from excessive invasion. Future identification of trophoblast ligands and their respective receptors on uterine Natural Killer cells and other leukocytes is likely to offer the best insight as to how this symbiotic state is achieved.


Subject(s)
Pregnancy/immunology , Female , Humans , Immune System/physiology , Killer Cells, Natural/immunology , Placenta/immunology , Trophoblasts/immunology
3.
Mol Hum Reprod ; 8(8): 776-84, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12149411

ABSTRACT

Human leukocyte antigen (HLA)-G, which is mainly expressed at the maternal-fetal interface, may play a role in the immune tolerance of the semi-allogenic fetus by the mother. Functional studies have shown that HLA-G is indeed a potential modulator of different immune responses. Therefore, it is of interest to study the level of expression of soluble HLA-G in several biological fluids derived from women with and without fertility problems. In order to measure soluble HLA-G, a reliable and sensitive HLA-G specific sandwich ELISA is required. Here, we describe such an ELISA in which G233 is used as the coating antibody and 56B as the detecting antibody. In comparison with two other assays, this assay shows highest responses to recombinant HLA-G and native HLA-G in primary trophoblast culture supernatant and high responses to HLA-G in amniotic fluid. No HLA-G in follicular fluid or preimplantation embryo culture supernatant could be detected.


Subject(s)
Enzyme-Linked Immunosorbent Assay , HLA Antigens/analysis , Histocompatibility Antigens Class I/analysis , Amniotic Fluid/metabolism , Antibodies, Monoclonal , Female , Follicular Fluid/metabolism , HLA-G Antigens , Humans
4.
Hum Mol Genet ; 10(10): 1093-100, 2001 May 01.
Article in English | MEDLINE | ID: mdl-11331620

ABSTRACT

Genomic imprinting is the phenomenon whereby mono-allelic expression of certain genes occurs depending on their parental origin. The observation that imprinting only occurs in placental mammals has led to the suggestion that it may play a role in this form of reproduction. In the present study we have investigated the pattern of expression of the human PEG3 gene in the early to term placenta, as well as the uterus and ovary, using RT-PCR, northern blot and in situ hybridization. A comparison is made with the expression of Peg3 in the mouse by histochemical staining in betageo knock out mice. We have demonstrated high levels of PEG3 in the human placenta and have localized the signal to the layer of villous cytotrophoblast cells. In contrast, the pattern of expression of Peg3 in the mouse placenta is less restricted, the message being present in all trophoblast populations. Thus, expression of PEG3/Peg3 in the human and mouse placenta is not directly comparable. We have also detected PEG3 message in the ovarian stroma. We have sequenced the human PEG3 gene from exon 3 to exon 9. By utilizing a polymorphism detected in exon 9, we have established that only the paternal allele is expressed in human placenta. Human PEG3 is therefore maternally imprinted as in mouse.


Subject(s)
Gene Expression Regulation, Developmental , Genomic Imprinting , Placenta/metabolism , Protein Kinases , Proteins/genetics , Transcription Factors , Amino Acid Sequence , Animals , Blotting, Northern , Embryo, Mammalian/metabolism , Exons , Female , Gene Expression Profiling , Humans , Introns , Kruppel-Like Transcription Factors , Mice , Mice, Knockout , Molecular Sequence Data , Ovary/metabolism , Pregnancy , Protein Biosynthesis , Sequence Analysis , Uterus/metabolism
5.
J Clin Endocrinol Metab ; 86(4): 1823-34, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11297624

ABSTRACT

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhagia and endometriosis. In pregnancy, failure of the endometrial spiral arterioles to undergo remodeling leads to preeclampsia. Here we report that in addition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was found in uterine nature killer cells in secretory phase endometrium and for Ang2 mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK cells did not induce human umbilical vein endothelial cell apoptosis. These results indicate that human endometrium expresses a wide range of angiogenic growth factors and that uterine nature killer cells may play an important role in the abnormal endometrial angiogenesis that underlies a range of disorders affecting women.


Subject(s)
Angiogenesis Inducing Agents/genetics , Killer Cells, Natural/metabolism , Proto-Oncogene Proteins , RNA, Messenger/metabolism , Uterus/metabolism , Angiogenesis Inducing Agents/metabolism , Angiopoietin-2 , Apoptosis/drug effects , Cells, Cultured , Culture Media, Conditioned/pharmacology , Cytochrome c Group/metabolism , Endothelial Growth Factors/genetics , Endothelium, Vascular/cytology , Endothelium, Vascular/physiology , Female , Humans , Interleukin-15/pharmacology , Interleukin-2/pharmacology , Killer Cells, Natural/cytology , Menstrual Cycle/physiology , Neoplasm Proteins/genetics , Placenta Growth Factor , Pregnancy Proteins/genetics , Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Receptor, TIE-1 , Receptor, TIE-2 , Receptors, Growth Factor/genetics , Receptors, Growth Factor/metabolism , Receptors, TIE , Receptors, Vascular Endothelial Growth Factor , Umbilical Veins/cytology , Umbilical Veins/physiology , Uterus/cytology , Vascular Endothelial Growth Factor C , Vascular Endothelial Growth Factor Receptor-3
6.
Am J Obstet Gynecol ; 184(5): 991-7, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11303210

ABSTRACT

OBJECTIVE: The aim of this study was to assess the use of circulating trophoblast cells in maternal peripheral blood for noninvasive prenatal diagnosis of numeric chromosomal aberrations. STUDY DESIGN: A combined procedure for immunocytochemical identification and deoxyribonucleic acid fluorescence in situ hybridization was used after a single enrichment step consisting of density gradient centrifugation. A specific HLA-G monoclonal antibody was used in combination with X and Y chromosome specific probes in deoxyribonucleic acid fluorescence in situ hybridization to confirm fetal identity of cells bearing HLA-G in the case of a male fetus. RESULTS: We detected fetal trophoblast cells expressing HLA-G in maternal blood starting at 9 weeks' gestation. In addition to fetal sex prediction with X and Y chromosome-specific probes, fetal aneuploidy was confirmed in peripheral blood from a pregnancy complicated by trisomy 21. CONCLUSION: Although the numbers of fetal cells were extremely low, the proof of concept was demonstrated. Early noninvasive prenatal screening for numeric chromosomal abnormalities with fetal trophoblast cells is feasible.


Subject(s)
HLA Antigens/biosynthesis , Histocompatibility Antigens Class I/biosynthesis , Pregnancy Trimester, First/immunology , Trophoblasts/immunology , Antibodies, Monoclonal , Centrifugation, Density Gradient , Chromosome Aberrations , Female , HLA Antigens/blood , HLA-G Antigens , Histocompatibility Antigens Class I/blood , Humans , Immunohistochemistry , Immunophenotyping , In Situ Hybridization, Fluorescence , Pregnancy , Prenatal Diagnosis/methods , Sex Determination Analysis , Trophoblasts/cytology , Trophoblasts/metabolism
7.
Am J Reprod Immunol ; 45(2): 103-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11216872

ABSTRACT

PROBLEM: It has been proposed that the expression of the non-classical MHC class I antigen, HLA-G, by trophoblast is one mechanism by which the placenta evades attack by maternal uterine NK cells. A similar mechanism is thought to be operative in the escape from immunosurveillance by tumor cells. However, data on the expression of HLA-G by tumor cells are highly conflicting. METHOD OF STUDY: In the present study, we have examined tissue sections from a wide variety of tumors by immunohistology and also several cell lines by flow cytometry and RT-PCR. Whilst very faint bands were detected in three cell lines (hepG2, Mead, CaSki) by RT-PCR, no tumors or cell lines were observed to express HLA-G protein. Furthermore, we found that tumor deposits are not usually infiltrated by NK cells. CONCLUSION: Our observations, therefore, do not support the proposal that tumor cells express HLA-G in order to evade host NK cell cytolysis.


Subject(s)
HLA Antigens/analysis , Histocompatibility Antigens Class I/analysis , Neoplasms/chemistry , HLA Antigens/genetics , HLA-G Antigens , Histocompatibility Antigens Class I/genetics , Humans , Immunohistochemistry , Leukocytes/physiology , Neoplasms/pathology , RNA, Messenger/analysis , Tumor Cells, Cultured
8.
Article in English | MEDLINE | ID: mdl-11023803

ABSTRACT

During implantation, the uterine decidua is invaded by extravillous trophoblast (EVT) cells whose function is to destroy the walls of the uterine spiral arteries in order to provide an adequate blood flow to the fetus. These EVT cells express an unusual combination of HLA class I molecules-HLA-C, HLA-E and HLA-G. The decidua is infiltrated by a population of natural killer (NK) cells with a distinctive phenotype of CD56(bright)CD16(-)CD3(-). These cells are particularly numerous in the decidua basalis at the implantation site where they come into close contact with invading EVT cells. These NK cells express a variety of receptors (CD94/NKG2, KIR and ILT) which are known to recognize HLA class I molecules. We believe that interaction between these NK cells and EVT cells provides the controlling influence for implantation.


Subject(s)
Embryo Implantation/immunology , Immunity, Cellular/physiology , Placenta/immunology , Female , Humans , Pregnancy , Sensitivity and Specificity , Trophoblasts/immunology
9.
Tissue Antigens ; 56(1): 30-7, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10958353

ABSTRACT

HLA-G is an effective ligand of natural killer (NK) inhibitory receptors, HLA-G transcripts have been detected in several human tumors, and cytokines like gamma interferon (IFN) enable HLA-G molecules to be expressed. These findings are particularly upsetting in case of melanomas: IFN treatment is frequently included in melanoma therapeutic protocols, and downregulation of classical class I molecules occurs in nearly half of these tumors. Therefore, a melanoma cell downregulating classical class I and de novo expressing HLA-G, either constitutively or upon IFN treatment, is probably a stealthy target for the immune system, having inhibited both the cytotoxic T lymphocyte (CTL) and the NK activity. To elucidate this point we have investigated the expression of HLA-G molecules in 45 melanoma cell lines before and after gammaIFN treatment. Analysis was performed by immunofluorescence and flow cytometry, using the anti-HLA-G MoAbs 87G and G233, by Western blot, using the anti-HLA-G MEM/G1 MoAb and PAG1 antiserum, and by RT-PCR analysis. In addition, 8 melanoma tissues from patients free from therapy and 6 nevi were studied by immunohistochemistry using the 87G MoAb. No evidence was gathered of HLA-G expression, neither constitutive nor, in cell lines, after gammaIFN treatment. We therefore conclude that HLA-G expression is an uncommon event in melanomas, and that a therapy including IFNs cannot harm the patient by inducing the de novo expression of HLA-G molecules at least in its G1 isoform.


Subject(s)
HLA Antigens/metabolism , Histocompatibility Antigens Class I/metabolism , Interferon-gamma/pharmacology , Melanoma/immunology , Antibodies, Monoclonal/immunology , Blotting, Western , Flow Cytometry , HLA Antigens/genetics , HLA Antigens/immunology , HLA-G Antigens , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Humans , RNA, Messenger/analysis , Tumor Cells, Cultured
10.
J Reprod Fertil Suppl ; 55: 83-90, 2000.
Article in English | MEDLINE | ID: mdl-10889837

ABSTRACT

The immunological relationship between the mammalian fetus and its mother during pregnancy has been considered similar to that between a transplanted allograft and its recipient. Hence, it has been assumed that implantation of the fetal placenta in the uterus would be controlled in a similar way by a maternal immune response mediated by T cells recognizing paternally derived alloantigens expressed by the placenta. However, recent evidence indicates that implantation might involve predominantly a novel allogeneic recognition system based on natural killer cells rather than T cells. The cellular and molecular basis of this local immune interaction between the fetal placenta and maternal uterus is the focus of intense research interest. As aberrant implantation can cause a variety of clinical problems including miscarriage, intrauterine growth retardation and pre-eclampsia, an understanding of the immunological mechanism by which this process is controlled could lead to the development of regimens to improve fetal growth and development.


Subject(s)
Embryo Implantation/immunology , Fetus/immunology , Killer Cells, Natural/immunology , Placenta/immunology , Pregnancy Complications/immunology , Cytokines/immunology , Female , HLA Antigens/immunology , Humans , Leukocytes/immunology , Macrophages/immunology , Pregnancy , Trophoblasts/immunology , Uterus/immunology
11.
Eur J Immunol ; 30(6): 1623-31, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10898498

ABSTRACT

Non-classical MHC class I molecule HLA-E is the ligand for CD94/NKG2 NK cell receptors. Surface expression of HLA-E requires binding of specific HLA class I leader sequences. The uterine mucosa in early pregnancy (decidua) is infiltrated by large numbers of NK cells, which are closely associated with placental trophoblast cells. In this study we demonstrate that trophoblast cells express HLA-E on their cell surface in addition to the previously reported expression of HLA-G and HLA-C. Furthermore, we show that the vast majority of decidual NK cells bind to HLA-E tetrameric complexes and this binding is inhibited by mAb to CD94. Thus, recognition of fetal HLA-E by decidual NK cells may play a key role in regulation of placentation. The functional consequences of decidual NK cell interaction were investigated in cytotoxicity assays using polyclonal decidual NK cells. The overall effect of CD94/NKG2 interaction with HLA-E is inhibition of cytotoxicity by decidual NK cells. However, since decidual NK cells are unable to kill trophoblast even in the presence of mAb to MHC class I molecules and NK cell receptors, HLA-E interaction with CD94/NKG2 receptors may regulate other functions besides cytolysis during implantation.


Subject(s)
Antigens, CD/metabolism , Decidua/cytology , HLA Antigens/metabolism , Histocompatibility Antigens Class I/metabolism , Killer Cells, Natural/metabolism , Lectins, C-Type , Membrane Glycoproteins/metabolism , Receptors, Immunologic/metabolism , Trophoblasts/metabolism , Cell Line , Cytotoxicity, Immunologic/immunology , Female , HLA Antigens/genetics , HLA-C Antigens/genetics , HLA-G Antigens , Histocompatibility Antigens Class I/genetics , Humans , Killer Cells, Natural/immunology , Ligands , NK Cell Lectin-Like Receptor Subfamily C , NK Cell Lectin-Like Receptor Subfamily D , Placenta/immunology , Placenta/metabolism , Pregnancy , Pregnancy Trimester, First , Receptors, Natural Killer Cell , Transfection , HLA-E Antigens
12.
Placenta ; 21 Suppl A: S81-5, 2000.
Article in English | MEDLINE | ID: mdl-10831129

ABSTRACT

During placentation the extravillous trophoblast (EVT) cells migrate through the decidua towards the maternal spiral arteries. The walls of the arteries are then destroyed by trophoblast resulting in an increased blood flow to the fetus. These EVT express HLA-G, HLA-E and HLA-C, an unusual combination of two non-classical and one classical MHC class I molecules. The decidua is infiltrated by distinctive uterine natural killer (NK) cells during the time of trophoblast invasion. These cells express a variety of receptors (CD94/NKG2, KIR and ILT) which are known to recognize HLA class I molecules. There is, therefore, a mechanism for molecular recognition of the placental trophoblast cells. The possible functional consequences of this uterine NK cell-trophoblast interactions are uncertain. One possible result is in an altered NK cell cytokine profile which modulates the invasive proclivity of the EVT. In this way placentation could be controlled.


Subject(s)
Decidua/immunology , Histocompatibility Antigens Class I/metabolism , Killer Cells, Natural/immunology , Receptors, Immunologic/metabolism , Trophoblasts/immunology , Decidua/cytology , Female , HLA Antigens/metabolism , HLA-C Antigens/metabolism , HLA-G Antigens , Humans , Placentation/immunology , Pregnancy , HLA-E Antigens
14.
Placenta ; 21(4): 376-87, 2000 May.
Article in English | MEDLINE | ID: mdl-10833373

ABSTRACT

In this paper definitive evidence that the classical class I product, HLA-C, is expressed on the surface of normal trophoblast cells is provided. HLA-C transcripts were sequenced from cDNA isolated from first trimester trophoblast cells obtained by flow cytometric sorting. Both paternal and maternal alleles were transcribed. HLA-C proteins were demonstrated by biochemical analysis and found on the cell surface in association with beta(2)-microglobulin. Upregulation of cell surface HLA-C but not HLA-G expression after interferon (IFN)-gamma treatment was demonstrated by flow cytometric analysis. Immunohistology has confirmed HLA-C is expressed by all extravillous subpopulations in vivo. The question of whether trophoblast HLA-C molecules interact with decidual NK cells expressing killer Ig-like receptors (KIR) has also been addressed. Our results demonstrate that extravillous trophoblast expresses at least two HLA class I molecules, HLA-G and HLA-C on the cell surface.


Subject(s)
HLA-C Antigens/biosynthesis , Trophoblasts/metabolism , Adult , Antigens, Surface/biosynthesis , Antigens, Surface/genetics , Choriocarcinoma/metabolism , Cytotoxicity Tests, Immunologic , Electrophoresis, Polyacrylamide Gel , Female , Flow Cytometry , Fluorescent Antibody Technique, Indirect , HLA Antigens/biosynthesis , HLA-C Antigens/genetics , HLA-G Antigens , Histocompatibility Antigens Class I/biosynthesis , Humans , Interferon-gamma/pharmacology , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Pregnancy , RNA, Messenger/biosynthesis , Receptors, Immunologic/immunology , Receptors, Immunologic/metabolism , Receptors, KIR , Receptors, KIR2DL1 , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Trophoblasts/drug effects , Tumor Cells, Cultured , Up-Regulation , beta 2-Microglobulin/metabolism
15.
Biochem Soc Trans ; 28(2): 196-8, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10816126

ABSTRACT

At the implantation site, the uterine mucosa (decidua) is infiltrated by large numbers of natural killer (NK) cells. These NK cells are in close contact with the invading fetal trophoblast and we have proposed that they might be the effector cells that control the implantation of the allogeneic placenta. Recent characterization of NK cell receptors and their HLA class I ligands has suggested potential mechanisms by which NK cells might interact with trophoblast. However, what happens as a result of this interaction is not clear. The traditional method for investigating NK cell function in vitro is the protection from lysis of target cells by expression of HLA class I antigens. This might not be an accurate reflection of what happens in vivo. Another function of NK cells is the production of cytokines on contact with target cells. This could be an important outcome of the interaction between decidual NK cells and trophoblast. Decidual NK cells are known to produce a variety of cytokines; trophoblast cells express receptors for many of these cytokines, indicating that they can potentially respond. In this way, decidual NK cells have a significant influence on trophoblast behaviour during implantation.


Subject(s)
Cytokines/biosynthesis , Decidua/cytology , Killer Cells, Natural/cytology , Killer Cells, Natural/metabolism , Trophoblasts/cytology , Trophoblasts/metabolism , Female , Histocompatibility Antigens Class I/metabolism , Humans , Ligands
16.
Biol Reprod ; 62(4): 959-68, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10727265

ABSTRACT

The natural killer (NK) cells that are present in the uterine mucosa (decidua) during early pregnancy have a distinctive phenotype, CD56(bright) CD16(-). These cells have previously been shown to proliferate and be activated by interleukin (IL)-2. However, IL-2 is absent from the decidua and placenta, and we have therefore investigated whether IL-15 is present in the uterus and can act on decidual NK cells. Both IL-15 mRNA and protein were found in a variety of cells but particularly in decidual macrophages. IL-15 induced a proliferative response in decidual NK cells that was blocked by anti-IL-15 and was augmented by stem cell factor. The cytolytic activity of decidual NK cells against K562 was augmented. Interestingly, in contrast to IL-2, although activation with IL-15 resulted in some killing of JEG-3 choriocarcinoma cells, normal trophoblast cells remained resistant to lysis. These findings suggest that IL-15 is a candidate cytokine responsible for NK cell proliferation in vivo in the progesterone-dominated secretory endometrium and early decidua.


Subject(s)
Decidua/metabolism , Interleukin-15/pharmacology , Killer Cells, Natural/metabolism , Receptors, Interleukin-2/biosynthesis , Adult , Cell Division/drug effects , Cell Line , Cell Survival/drug effects , Decidua/cytology , Decidua/drug effects , Female , Flow Cytometry , Humans , Interleukin-12/biosynthesis , Interleukin-12/pharmacology , Interleukin-15/metabolism , Interleukin-18/pharmacology , Killer Cells, Natural/drug effects , Phenotype , Placenta/drug effects , Placenta/metabolism , Pregnancy , RNA, Messenger/biosynthesis , Receptors, Interleukin-15 , Receptors, Interleukin-2/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Stem Cell Factor/pharmacology , Trophoblasts/drug effects
17.
Hum Immunol ; 61(3): 212-24, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10689111

ABSTRACT

In contrast to HLA class Ia, the HLA-G class Ib transcripts can be alternativeley spliced to yield several isoforms including four potentially membrane-bound variants, namely HLA-G1, -G2, -G3 and G4. It is so far unclear whether each of these splice variants lacking one or two external domains is properly translated and expressed at the cell surface. We used targeted Enhanced Green Fluorescence Protein (EGFP)-HLA-G fusion cDNA to track HLA-G isoform expression in living murine (L-human beta2m) and human (JAR) transiently transfected cells. It was demonstrated that the four HLA-G1, -G2, -G3, and -G4 isoforms were translated in these transfectants by the means of (i) Western blotting analysis, using an anti-EGFP mAb; (ii) intracellular double labeling flow cytometry analysis, using the EGFP natural fluorescence and phycoerythrin-labeled HCA2 anti-HLA-G mAb; and (iii) immunocytochemistry on isolated acetone fixed transfectants with the use of different anti-HLA-G mAbs. Cell surface flow cytometry analysis using the HCA2 mAb revealed that only the HLA-G1 isoform was expressed as a membrane-bound protein. Two color confocal microscopy performed on fixed, permeabilized cells further showed that the EGFP green fluorescence co-localized with anti-calnexin rhodamine fluorescence in the four HLA-G isoform transfectants but only in HLA-G1 transfectant was the green EGFP fluorescence also detectable at the outer part of the cells, suggesting that the HLA-G2, -G3, and G4 were retained in the endoplasmic reticulum. Such intracellular retention of the three shorter forms of HLA-G suggest that they may play a role in regulating cell surface expression either of the full length HLA-G1 form or of HLA-E.


Subject(s)
HLA Antigens/biosynthesis , Histocompatibility Antigens Class I/biosynthesis , Membrane Proteins/biosynthesis , Animals , Biological Transport , Endoplasmic Reticulum/metabolism , HLA Antigens/genetics , HLA-G Antigens , Histocompatibility Antigens Class I/genetics , Humans , Membrane Proteins/genetics , Mice , Protein Biosynthesis , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , Recombinant Proteins/biosynthesis , Transfection
18.
J Immunol ; 163(9): 4651-4, 1999 Nov 01.
Article in English | MEDLINE | ID: mdl-10528161

ABSTRACT

Transmembrane adapter proteins are a class of molecules that mediate signals from an extracellular receptor to the cytoplasm of the cell. We have cloned a novel transmembrane adapter protein called KAP10, a approximately 10-kDa protein that is encoded within 100 bp of the DAP12 locus on human chromosome 19. KAP10 is predominantly expressed in immune cells, including NK cells, T cells, and monocytes. We show that KAP10, unlike other transmembrane adapter proteins, binds phosphatidylinositol-3 kinase following phosphorylation of a cytoplasmic YINM motif, which results in activation of Akt. In addition, we identify KAP10 as being able to bind the adapter protein Grb2. Based on our data, we suggest that this molecule is involved in stimulation and costimulation in cells of both myeloid and lymphoid origin.


Subject(s)
Membrane Proteins/genetics , Membrane Proteins/metabolism , Proto-Oncogene Proteins , Receptors, Immunologic/genetics , Signal Transduction/immunology , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Animals , Base Sequence , CD4 Antigens/immunology , Cell Line , Cell Lineage/genetics , Cell Lineage/immunology , Enzyme Activation , Genetic Linkage/immunology , Hematopoietic Stem Cells/metabolism , Humans , Immune Sera/metabolism , Jurkat Cells , Lymphoid Tissue/cytology , Lymphoid Tissue/metabolism , Membrane Proteins/biosynthesis , Membrane Proteins/immunology , Mice , Molecular Sequence Data , Phosphatidylinositol 3-Kinases/metabolism , Protein Binding/immunology , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt , Receptors, Immunologic/metabolism , Signal Transduction/genetics , U937 Cells
20.
Hum Reprod ; 14(8): 2131-8, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10438439

ABSTRACT

The remodelling of the maternal uterine spiral arteries during pregnancy, known as physiological change, is critical for the normal growth and development of the fetus. Controversy has surrounded the part played by fetal trophoblast in the transformation of these spiral arteries. To address this debate, a histological and immunochemical comparison of blood vessels from the implantation sites of human pregnancies of early gestation with uterine tissue where trophoblast was absent was performed. Results showed that true physiological change, with the features of medial necrosis and deposition of fibrinoid material, only occurred in the presence of trophoblast. In addition, it was found that subpopulations of trophoblast contribute differently in the process. Interstitial trophoblast-mediated destruction of the arterial media precedes replacement of the endothelial cells by endovascular trophoblast.


Subject(s)
Arteries/physiology , Decidua/blood supply , Pregnancy/physiology , Trophoblasts/physiology , Arteries/cytology , Female , Humans
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