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M Colonna

Publications and source records attributed to M Colonna.

At least 73 records · Page 4Linked to original sources
PubMed1999

Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties.

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.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Tetrameric complexes of human histocompatibility leukocyte antigen (HLA)-G bind to peripheral blood myelomonocytic cells.

The nonclassical MHC class I molecule human histocompatibility leukocyte antigen (HLA)-G is selectively expressed on fetal trophoblast tissue at the maternal-fetal interface in pregnancy. It has long been suggested that HLA-G may inhibit maternal natural killer (NK) cells through interaction with particular NK cell receptors (KIRs). To investigate interactions of HLA-G, we constructed phycoerythrin-labeled tetrameric complexes of HLA-G refolded with a self-peptide. These HLA-G tetramers failed to bind to NK cells and cells transfected with CD94/NKG2 and killer immunoglobulin-like NK receptors. In contrast, HLA-G tetramers did bind to peripheral blood monocytes, staining a CD16(+)CD14(mid) subset with greater intensity. On transfectants, HLA-G tetramers bound to inhibitory immunoglobulin-like transcript (ILT)2 and ILT4 receptors. However, staining in the presence of antibodies reactive with ILT receptors revealed that the interaction of HLA-G tetramers with blood monocytes was largely due to binding to ILT4. These results suggest that the primary role of HLA-G may be the modulation of myelomonocytic cell behavior in pregnancy.

Animals↗
PubMed1999

Human myeloid cells express an activating ILT receptor (ILT1) that associates with Fc receptor gamma-chain.

Ig-like transcripts (ILTs) encode cell surface receptors expressed on myeloid and lymphoid cells that are structurally and functionally related to killer cell inhibitory receptors. One ILT, designated ILT1, contains a short cytoplasmic domain that lacks sequence motifs implicated in signal transduction. Its function is unknown. Similar short cytoplasmic domains have been observed in activating NK cell receptors and FcalphaR, which transduce stimulatory signals via associated DAP12 and FcepsilonRIgamma proteins, respectively. Here we show that ILT1 receptor is selectively expressed on myeloid cells, functions as an activating receptor, and associates with FcepsilonRIgamma rather than DAP12.

Animals↗
PubMed1999

The ILT2(LIR1) and CD94/NKG2A NK cell receptors respectively recognize HLA-G1 and HLA-E molecules co-expressed on target cells.

Previous studies on NK recognition of HLA-G1 employed as targets 721.221 transfectants (.221-G1) that unknowingly co-expressed the HLA-E molecule, subsequently found to be a major ligand for the CD94/NKG2 receptors. In the present study we re-evaluated the relative role played by CD94/NKG2 and ILT2(LIR1) molecules in recognition of HLA-G1 by NK clones. We employed as targets .221-G1 cells and a surface HLA-E-negative transfectant, .221-G1(Eneg), generated by site-directed mutagenesis of the HLA-G1 leader sequence. The antagonistic effects of receptor- (ie. CD94/NKG2A, ILT2) and ligand-specific mAb (i.e. HLA-G, HLA-E) were assessed. In addition, binding of an ILT2-Ig fusion protein to the .221-AEH, expressing only HLA-E, and the .221-G1(Eneg) transfectants was analyzed. Our data demonstrate that NK recognition of cells expressing HLA-G1 involves at least two non-overlapping receptor-ligand systems: the CD94/NKG2 interaction with HLA-E, and the engagement of the ILT2(LIR1) receptor by HLA-G1 molecules.

Antibodies, Monoclonal↗
PubMed1999

Activating interactions in human NK cell recognition: the role of 2B4-CD48.

2B4 is a cell surface glycoprotein of the immunoglobulin superfamily structurally related to CD2-like molecules. It was originally identified in the mouse as a receptor that mediates non-MHC-restricted cytotoxicity by NK cells and CD8+ T cells. Recently, 2B4 was shown to bind CD48 by molecular binding assays and surface plasmon resonance. Here, we have investigated the cell surface expression, biochemical characteristics and function of human 2B4. Our results show that 2B4 is expressed not only on NK cells and CD8+ T cells, but also on monocytes and basophils, indicating a broader role for 2B4 in leukocyte activation. In NK cells, engagement of 2B4 with a specific monoclonal antibody or with CD48 can trigger NK cell-mediated cytotoxicity. The contribution of 2B4-CD48 interaction to target cell lysis by different NK cell clones varies, probably dependent on the relative contribution of other receptor-ligand interactions. In T cells and monocytes, ligation of 2B4 does not lead to T cell or monocyte activation. Thus, it appears that the primary function of 2B4 is to modulate other receptor-ligand interactions to enhance leukocyte activation.

Amino Acid Sequence↗
PubMed1999

Identification of the CD85 antigen as ILT2, an inhibitory MHC class I receptor of the immunoglobulin superfamily.

The CD85 molecule was originally defined at the Fifth Workshop on Leucocyte Antigens in 1993 by two monoclonal antibodies, VMP55 and GHI/75. This cell-surface glycoprotein is expressed on B cells, monocytes, and subpopulations of T and natural killer (NK) cells, and particularly high levels are expressed by normal and neoplastic plasma cells and by hairy cell leukemia B cells. We affinity purified the CD85 antigen and obtained tryptic peptide sequence which indicated that this molecule might be ILT2, a recently described inhibitory major histocompatibility complex class I receptor of the immunoglobulin superfamily. This was confirmed by showing that both of the original anti-CD85 mAbs stained ILT2 transfectants. The cell signaling role demonstrated for ILT2 is consistent with the previously reported involvement of CD85 in T cell activation.

Antibodies, Monoclonal↗
PubMed1999

A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells.

We review what is presently known about structure, cellular distribution, biochemical characteristics, and function of a new family of human cell-surface receptors referred to as immunoglobulin-like transcripts (ILTs), leukocyte Ig-like receptors (LIRs), or monocyte/macrophage Ig-like receptors (MIRs). These receptors are genetically, structurally, and functionally related to a group of natural killer (NK) cell receptors for HLA class I molecules known as killer cell Ig-like receptors (KIRs). Distinct ILT/LIR/MIR isotypes are differentially expressed on lymphocytes, monocytes, macrophages, dendritic cells, and granulocytes; at least some of them recognize HLA class I molecules. Whereas some isotypes either inhibit or induce cell activation, others may be secreted as soluble receptors. ILT/LIR/MIR receptors may allow all immune cells to monitor class I expression on other cells and to respond in its absence, just as NK cells do. In addition, they may contribute to homeostasis by establishing activation thresholds that can be overcome only by relevant triggering stimuli and not by bystander cells.

Antibodies, Monoclonal↗
PubMed1999

Inhibitory and activating receptors involved in immune surveillance by human NK and myeloid cells.

We review the structure, cellular distribution, ligand specificity, and function of two emerging types of receptors involved in natural killer (NK) and myeloid cell recognition of other cells: ILT/LIR/MIR and 2B4 receptors. ILT/LIR/MIR receptors are differentially expressed on lymphoid and myeloid cells and two of them, ILT2 and ILT4, recognize HLA class I molecules. Whereas some receptors inhibit, others induce cell activation. 2B4 is broadly expressed on leukocytes, binds CD48, and mediates non-MHC-restricted cytotoxicity by NK cells.

Antigens, CD↗
PubMed1999

Organization of the leukocyte receptor cluster (LRC) on human chromosome 19q13.4.

A large number of cDNAs coding for killer cell inhibitory receptors (KIR) and immunoglobulin-like transcripts (ILT) have already been described, and some of the respective genes are known to map in 19q13.4. To understand the genetic relationships of these transcripts, some of which may be alleles from polymorphic loci, it is necessary to determine the genomic organization of the region. To do so, we performed long-range restriction enzyme mapping of the 19q13.4 region along with YAC and PAC contig construction. Eighteen genes could be assigned to a chromosomal segment of about 600 kb. Twelve KIR loci are contained within approximately 200 kb, bordered by the locus for the Fc receptor for IgA (FCAR) at the telomeric side and by a 150-kb cluster containing ILT loci at the centromeric side. A further region with a maximal size of 135 kb containing at least one ILT gene was identified further centromeric, separated by approximately 50 kb from the ILT region near the KIR cluster. The entire KIR/ILT region revealed a considerable degree of genetic polymorphism as shown, for example, by different restriction maps of two sets of PACs spanning the same region. We suggest the designation "Leukocyte Receptor Cluster" (LRC) for this chromosomal segment.

Antigens, CD↗
PubMed1999

Pathological prognostic factors in a series of 137 stage I TNM/UICC endometrial carcinomas.

PURPOSE: We report on the long-term results of combination surgery-radiotherapy in cT1 carcinoma of the endometrium according to prognostic factors. PATIENTS AND METHODS: From 1974 to 1993, 130 women suffering from cT1Nx-O Mo endometrial carcinoma, underwent surgical resection. The median age was 62 years. Thirteen received pre-operative irradiation, two pre-operative brachytherapy followed by post-operative external irradiation and 115 patients (88.35%) underwent post-operative irradiation therapy by brachytherapy or external beam irradiation. RESULTS: The median follow-up is 67 months. Overall and specific survival rates for patients with cT1pT1 tumours were 71.1 and 85% at 10 years. For overall survival, lymph node invasion was the most powerful prognostic factor in the multivariate analysis (P = 0.02). If lymph node invasion is not taken into account, the WHO histological grade exerts a significant prognostic impact (P = 0.001). CONCLUSION: For stage cT1 endometrial carcinoma, primary surgery allows radiotherapy to be adjusted according to the WHO histological grade, myometrial invasion and the pelvic lymph node status.

Adult↗
PubMed1999

DAP12: a key accessory protein for relaying signals by natural killer cell receptors.

DAP12 is a 12 kDa transmembrane protein recently recognized as a key signal transduction receptor element in Natural Killer (NK) cells. It is a disulfide-linked homodimer that non-covalently associates with several activating receptors expressed on NK cells. Activation signals initiated through DAP12 are predicted to play strategic roles in triggering NK cell cytotoxicity responses toward certain tumor cells and virally infected cells. The cytoplasmic domain of DAP12 contains an Immunoreceptor Tyrosine-based Activation Motif (ITAM). Phosphorylation of ITAM tyrosines mediates associations with protein tyrosine kinases, which is a resonant feature of signalling through these motifs in T and B cell antigen receptors. In addition, its expression in other tissues, including dendritic cells and monocytes, suggests that DAP12 transduces ITAM-mediated activation signals for an extended array of receptors in those cells as well.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4.

Natural killer (NK) cells spontaneously detect and kill cancerous and virally infected cells through receptors that transduce either activating or inhibiting signals. The majority of well studied NK receptors are involved in inhibitory signaling. However, we have previously described an activating receptor, 2B4, expressed on all murine NK cells and a subset of T cells that mediate non-major histocompatibility complex (MHC) restricted killing. Anti-2B4 monoclonal antibodies directed against IL-2-activated NK cells enhanced their destruction of tumor cells. Recently, we determined binding of 2B4 to CD48 with a much higher affinity than CD2 to CD48. Here we describe the molecular characterization of a cDNA clone homologous to mouse 2B4, isolated from a human NK cell library. The cDNA clone contained an open reading frame encoding a polypeptide chain of 365 amino acid residues. The predicted protein sequence showed 70% similarity to murine 2B4. Additionally, it has 48, 45, and 43% similarity to human CD84, CDw150 (SLAM), and CD48, respectively. RNA blot analysis indicates the presence of 3 kb and 5 kb transcripts in T- and NK-cell lines. A single transcript of 3 kb is identified in poly(A)+ RNA from human spleen, peripheral blood leukocytes, and lymph node, whereas, the level of expression in bone marrow and fetal liver was indeterminate. Preliminary functional data suggests that NK-cell interaction with target cells via 2B4 modulates human NK-cell cytolytic activity.

Amino Acid Sequence↗
PubMed1999

Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon.

We have identified two cell subsets in human blood based on the lack of lineage markers (lin-) and the differential expression of immunoglobulin-like transcript receptor 1 (ILT1) and ILT3. One subset (lin-/ILT3+/ILT1+) is related to myeloid dendritic cells. The other subset (lin-/ILT3+/ILT1+) corresponds to 'plasmacytoid monocytes'. These cells are found in inflamed lymph nodes in and around the high endothelial venules. They express CD62L and CXCR3, and produce extremely large amounts of type I interferon after stimulation with influenza virus or CD40L. These results, with the distinct cell phenotype, indicate that plasmacytoid monocytes represent a specialized cell lineage that enters inflamed lymph nodes at high endothelial venules, where it produces type I interferon. Plasmacytoid monocytes may protect other cells from viral infections and promote survival of antigen-activated T cells.

Antigens, CD↗
PubMed1999

Analysis and classification of interval cancers in a French breast cancer screening programme (département of Isère).

The objective of this study is to analyse detection rates and stage of diagnosis of interval cancers in the mass screening mammography programme of Isère (France), launched in 1990. Interval cancers are defined as breast cancers diagnosed within 30 months after a negative screening assessment, for women attending the programme between November 1990 and December 1994. Stages of diagnosis of these cancers are compared with those of screened cancers and to those of cancers diagnosed outside the programme. The rates of invasive interval cancers are 17.7% of the expected incidence rate during the first year, 60.0% during the second year and 58.8% after the second year. Sensitivity of the programme (one test every 30 months) is 74%; sensitivity at one year is 82%. Results are better for women aged 60-69 years than for younger women (50-59 years). Diagnosis is made at an early stage with 8% of in situ cases, and with 40% of very small tumours (sizes < or = 10 mm). Those stages are very close to the ones for screened cases. Interval cancer rates are low during the first year. Higher rates for the second year and early stages of diagnosis could be explained by self-referred screening practice in our area.

Age Distribution↗
PubMed1999

Lyapunov exponents in unstable systems.

We investigate the dynamical behavior of unstable systems in the vicinity of the critical point associated with a liquid-gas phase transition. By considering a mean-field treatment, we first perform a linear analysis and discuss the instability growth times. Then, coming to complete Vlasov simulations, we investigate the role of nonlinear effects and calculate the Lyapunov exponents. As a main result, we find that near the critical point, the Lyapunov exponents exhibit a power-law behavior, with a critical exponent beta=0.5. This suggests that in thermodynamical systems the Lyapunov exponent behaves as an order parameter to signal the transition from the liquid to the gas phase.

Journal Article↗
PubMed1999

Cancer registry data based estimation of regional cancer incidence: application to breast and colorectal cancer in French administrative regions.

STUDY OBJECTIVE: In many countries, cancer registries cover only a small part of the national population. Cancer incidence for the rest of the country has therefore to be estimated. This can be done from mortality data using the relation between incidence and mortality observed in the cancer registry areas. Such an approach was used to study geographical variation and trend of colorectal and breast cancer incidence in France where 10% of the national population is covered by cancer registries. DESIGN: This study applies the incidence/mortality ratios of cancer registry areas to regional mortality data to obtain an estimation of cancer incidence at a given point in time. Age and period effects are included in the statistical models. MAIN RESULTS: The incidence estimations are given for 21 administrative regions and three time points (1985, 1990, 1995). The European standardised incidence rates for breast cancer ranged from 86.8 to 128.8. For colorectal cancer, these rates ranged from 48.2 to 79.6 for men, and from 32.5 to 48.8 for women. Breast cancer incidence has increased considerably between 1985 and 1995 with a higher increase in the north than in the south of France. The incidence of colorectal cancer has also increased, albeit to a lesser extent. CONCLUSION: The incidence estimation method proposed leads to regional incidence rates that are useful for planning health care services on a regional basis and may also be used to study regional differences in incidence. This method is useful when only partial incidence data are available.

Adult↗
PubMed1999

[Patterns of health care delivery and breast cancer in the department of Isère in 1955].

BACKGROUND: Caring for cancer patients is expensive, warranting verification that health care organization works in a satisfactory way. A first step of this evaluation deals with the description of the pathway followed in the health care system by the patient. METHODS: 671 breast cancer cases were diagnosed in Isère in 1995. According to the place where each treatment (surgery, chemotherapy, radiotherapy) was performed, we described pathways for the patient, either entirely private, public or mixed. Characteristics of the patient (age, place of residence), of the disease (extent of disease, way of discovery) and of the physician (general practitioner, specialist) might have influenced the choice of this pathway. We described and tested the distribution of these characteristics within the 3 groups using univariate analysis. Relative risk of being affected to the private pathway compared to the public one was computed, after adjusting for age, type of physician, extent of disease, way of discovery and sanitary area, using a multivariate analysis (logistic regression). RESULTS: In the department of Isère, the private pathway cared for 55% of breast cancers, the public one 23% and the mixed one 19%. There was no preferential recruitment according to age, physician type, presence of metastasis or of the rural or urban residence. In sanitary area number 5, characterized by an important attraction of the patients by the nearby department of Rhône, 41% of the patients were cared for the private pathway, compared to 63% in sanitary area 4, where most patients were treated in the main town of Isère: Grenoble. After early breast cancer detection with mammography instead of breast cancer screening, probability of being cared for in the private pathway was 2-fold higher (OR = 2) than in the public one. CONCLUSION: In Isère department, early breast cancer detection with mammography is in favor of the private pathway. This is not true for physician type, neither for characteristics of the patient or extent of the disease. Finally, the distance to next department of oncology or radiotherapy plays a major role.

Aged↗