The Experts below are selected from a list of 1777350 Experts worldwide ranked by ideXlab platform

Angel L. Corbí - One of the best experts on this subject based on the ideXlab platform.

  • identification of sp1 binding sites in the CD11c p150 95α and CD11a lfa 1α integrin subunit promoters and their involvement in the tissuespecific expression of CD11c
    European Journal of Immunology, 1995
    Co-Authors: Cristina Lopezrodriguez, Huimin Chen, Daniel G Tenen, Angel L. Corbí
    Abstract:

    The leukocyte integrins LFA-1 (CD11a/CD18) and p150,95 (CD11c/CD18) mediate cell-cell and cell-extracellular matrix interactions during inflammatory responses and signal transduction into the cytoplasm. While the CD11a integrin subunit is expressed on all leukocytes, CD11c is almost exclusively expressed on cells of the myeloid lineage and on activated B lymphocytes. Its expression is regulated during cell activation and differentiation by transcriptional mechanisms. We have previously demonstrated that the proximal region of the CD11c promoter directs tissue-restricted and developmentally-regulated expression of reporter genes. Structural studies by electrophoretic mobility shift assays have demonstrated the presence of two Sp1-binding sites at -70 (Sp1-70) and -120 (Sp1-120) which mediate the Sp1 transactivation of the CD11c promoter in Sp1-defective SL2 cells, and which are involved in cell lineage-specific DNA-protein interactions, as demonstrated by footprinting in vivo. More importantly, mutation of either Sp1 site inhibited the activity of the CD11c promoter both in myeloid U937 cells and the CD11c-expressing B lymphoblastoid JY cell line, while the opposite effect was observed in the CD11c-negative epithelial HeLa cell line, demonstrating the involvement of both Sp1-binding sites in the basal and the tissue-restricted expression of the CD11c integrin subunit gene. Interestingly, the analysis of the CD11a proximal promoter also revealed the existence of an Sp1-binding site at -70, indicating a common role for these cis-acting elements in the transcription of the leukocyte integrin alpha subunit genes. The binding of Sp1 to the regulatory regions of the leukocyte integrin genes raises the possibility that the retinoblastoma susceptibility gene product is implicated in integrin expression through its functional interaction with Sp1, thus establishing a link between integrin-dependent leukocyte adhesiveness and the state of cellular differentiation/proliferation.

  • hematopoietic cell type dependent regulation of leukocyte integrin functional activity CD11b and CD11c expression inhibits lfa 1 dependent aggregation of differentiated u937 cells
    Cellular Immunology, 1995
    Co-Authors: Arsenio Nueda, Cristina Lopezrodriguez, Miguel Rubio, M Sotillos, Antonio Postigo, M A Del Pozo, Miguel A Vega, Angel L. Corbí
    Abstract:

    To study the influence of the cellular environment on the functional activity of leukocyte integrins and to analyze their involvement in hematopoietic cell differentiation, we have developed stable transfectants of LFA-1, Mac-1, and p150,95 (CD11a-c/CD18) leukocyte integrins in cultured cell lines whose differentiation can be induced in vitro. As on circulating leukocytes, the integrins expressed on U937 or K562 cells were expressed in a constitutively inactive state, as demonstrated by the lack of adhesion to their cellular counterreceptors or soluble ligands, the absence of CD18-dependent intercellular aggregation, and their inability to mediate adhesion to protein-coated plates. However, while leukocyte integrin adhesive functions in U937 cells were induced upon treatment with cellular agonists (e.g., PMA), their function in K562 cells could be upregulated only with activating monoclonal antibodies, demonstrating the cell-type-specific regulation of the adhesive capabilities of the three leukocyte integrins in hematopoietic cellular environment. On the other hand, the expression of either CD11b/CD18 or CD11c/CD18 in U937 myeloid cells before induction of differentiation greatly affected the adhesive phenotype of differentiating cells by abrogating the CD11a/CD18-CD54-dependent homotypic aggregation. Unlike that of mock-transfected U937 cells, differentiation of CD11b/CD18- or CD11c/CD18-transfected U937 cells led to cell adhesion and spreading on the tissue culture plates, with an almost total absence of homotypic aggregates. These results confirm the role of CD11b/CD18 and CD11c/CD18 in myeloid cell adhesion and spreading and suggest that the CD11b/- and CD11c/CD18-mediated recognition of substrate-bound ligands competes or interferes with LFA-1-dependent intercellular adhesion.

  • CD23 Regulates monocyte activation through a novel interaction with the adhesion molecules CD11b-CD18 and CD11c-CD18
    Immunity, 1995
    Co-Authors: Sybille Lecoanet-henchoz, Angel L. Corbí, Jean-françois Gauchat, Jean-pierre Aubry, Pierre Graber, Paul Life, Nathalie Paul-eugène, Bernard Ferrua, B. Dugas, Christine Plater-zyberk
    Abstract:

    Abstract CD23 is expressed on a variety of haemopoietic cells and displays pleiotropic activities in vitro. We report that in addition to CD21 and IgE, CD23 interacts specifically with the CD11b and CD11c, the α chains of the β2 integrin adhesion molecule complexes CD11b-CD18 and CD11c-C1318, on monocytes. Full-length recombinant CD23 incorporated into fluorescent liposomes was shown to bind to COS cells transfected with cDNA encoding either CD11b-CD18 or CD11c-CD18 but not with CD11a-CD18. The Interaction was specifically inhibited by anti-CD11b or anti-CD11c, respectively, and by anti-CD23 MAbs. The functional significance of this ligand pairing was demonstrated by triggering CD11b and CD11c on monocytes with either recombinant CD23 or anti-CD11b and anti-CD11c MAbs to cause a marked increase in nitrite-oxidative products and proinflammatory cytokines (IL-1β, IL-6, and TNFα). These CD23-mediated activities were decreased by Fab frogments of MAbs to CD11b, CD11c, and CD23. These results demonstrate that CD11b and CD11c are receptors for CD23 and that this novel ligand pairing regulates important activities of monocytes.

S Alex K Law - One of the best experts on this subject based on the ideXlab platform.

  • genetic analysis of patients with leukocyte adhesion deficiency genomic sequencing reveals otherwise undetectable mutations
    Experimental Hematology, 2002
    Co-Authors: Dirk Roos, Christof Meischl, Martin De Boer, S Simsek, R S Weening, Ozden Sanal, Ilhan Tezcan, Tayfun Gungor, S Alex K Law
    Abstract:

    Abstract Objective. The aim of this study was to analyze mutations in DNA from patients with leukocyte adhesion deficiency (LAD), an immunodeficiency caused by absence of the β 2 subunit (CD18) of the leukocyte integrins LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), p150,95 (CD11c/CD18), and CR4 (CD11d/CD18). Methods. We developed genomic DNA PCR sequencing to detect mutations not only in exons but also in introns. Results. Eight LAD patients were analyzed, of which five had homozygous mutations, i.e., a 0.8-kb deletion, a branchpoint mutation in intron 5 causing mRNA missplicing, a nonsense mutation, and two missense mutations. Four of these mutations are novel. We cotransfected the two mutant CD18 proteins with normal CD11a, b, or c in COS cells. This resulted in absence of all three β 2 integrins on the surface of cells transfected with CD18 252Arg . However, CD18 593Cys supported some LFA-1 and p150,95 formation in COS cells. The other three patients were compound heterozygotes in which only one allele had previously been characterized, because the other alleles were undetectable at the cDNA level. We identified the unknown mutations as a novel two-nucleotide deletion, a nonsense mutation, and a single nucleotide deletion. Conclusion. Our method allows identification of mutations in CD18 from genomic DNA. This opens the possibility of early prenatal diagnosis of LAD and reliable carrier detection.

  • effect of integrin beta 2 subunit truncations on lfa 1 CD11a cd18 and mac 1 CD11b cd18 assembly surface expression and function
    Journal of Immunology, 2000
    Co-Authors: Suetmien Tan, Robert H Hyland, Aymen Alshamkhani, Wendy A Douglass, J Shaw, S Alex K Law
    Abstract:

    LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) are members of the beta2 integrins involved in leukocyte function during immune and inflammatory responses. We aimed to determine a minimized beta2 subunit that forms functional LFA-1 and Mac-1. Using a series of truncated beta2 variants, we showed that the subregion Q23-D300 of the beta2 subunit is sufficient to combine with the alphaL and alphaM subunits intracellularly. However, only the beta2 variants terminating after Q444 promote cell surface expression of LFA-1 and Mac-1. Thus, the major cysteine-rich region and the three highly conserved cysteine residues at positions 445, 447, and 449 of the beta2 subunit are not required for LFA-1 and Mac-1 surface expression. The surface-expressed LFA-1 variants are constitutively active with respect to ICAM-1 adhesion and these variants express the activation reporter epitope of the mAb 24. In contrast, surface-expressed Mac-1, both the wild type and variants, require 0. 5 mM MnCl2 for adhesion to denatured BSA. These results suggest that the role of the beta2 subunit in LFA-1- and Mac-1-mediated adhesion may be different.

Carl G Figdor - One of the best experts on this subject based on the ideXlab platform.

  • competition between lymphocyte function associated antigen 1 CD11a cd18 and mac 1 CD11b cd18 for binding to intercellular adhesion molecule 1 cd54
    Journal of Leukocyte Biology, 1996
    Co-Authors: M Lub, Y Van Kooyk, Carl G Figdor
    Abstract:

    Both human integrin receptors Mac-1 (CD11b/CD18,CR3)and lymphocyte function-associated antigen (LFA)-1 (CD11a/CD18) have been demonstrated to bind human intercellular adhesion molecule-1 (ICAM-1) (CD54). Here we show that LFA-1 and Mac-1 can bind to ICAM-1 in the mouse as well. Interestingly, we observed that binding of murine LFA-1 dominates over Mac-1 for binding to ICAM-1. Using three different murine macrophage cell lines that express distinct levels of LFA-1 and Mac-1 on their cell surface, we could only detect Mac-1-dependent adhesion to ICAM-1 when little or no LFA-1 is expressed on the cell surface. When LFA-1 and Mac-1 are expressed at similar levels, the LFA-1/ICAM-1 interaction dominates over Mac-1/ICAM-1 interaction, indicating that there is a competition of LFA-1 and Mac-1 for ICAM-1 binding.

  • antibodies that selectively inhibit leukocyte function associated antigen 1 binding to intercellular adhesion molecule 3 recognize a unique epitope within the CD11a i domain
    Journal of Biological Chemistry, 1996
    Co-Authors: M E Binnerts, Caroline P Edwards, Sarah C Bodary, Mark Champe, Y Van Kooyk, L Presta, Carl G Figdor, Phillip W Berman
    Abstract:

    Several studies indicate that the I domain located in the alpha chain (CD11a) of leukocyte function-associated antigen-1 (LFA-1; CD11a/CD18) plays an essential role in ligand recognition. We recently identified three distinct epitopes (IdeA, IdeB, and IdeC) within the CD11a I domain, recognized by antibodies that block binding of LFA-1 to intercellular adhesion molecules (ICAM) 1, 2, and 3. In the present study, we used a series of human/murine CD11a I domain chimeras, to localize a fourth I domain epitope (IdeD), recognized by three independently derived anti-CD11a antibodies that selectively block the binding of LFA-1 to ICAM-3, but not to ICAM-1. The IdeD epitope depended on human CD11a residues Asp182 and Ser184 and was not present in CD11b or CD11c. Although mutation of Asp182 and Ser184 failed to abolish ICAM-3 adhesion of LFA-1 transfectants, alignment of these residues with the crystal structure of the CD11a I domain suggested that the IdeD epitope is located in close proximity to residues (Ile126 and Asn129) recently implicated in the ICAM-3 binding site. Interestingly, the IdeB and IdeC epitopes appeared to be in close proximity of a divalent cation binding pocket within the CD11a I domain that regulates both ICAM-1 and ICAM-3 adhesion. Taken together, these data indicate that distinct regions of the CD11a I domain contain epitopes for antibodies that either selectively inhibit binding of LFA-1 to ICAM-3, or interfere with both ICAM-1 and ICAM-3 binding of LFA-1.

Carl G Gahmberg - One of the best experts on this subject based on the ideXlab platform.

Zsuzsa Bajtay - One of the best experts on this subject based on the ideXlab platform.

  • the role of cr3 CD11b cd18 and cr4 CD11c cd18 in complement mediated phagocytosis and podosome formation by human phagocytes
    Molecular Immunology, 2017
    Co-Authors: Szilvia Lukácsi, Noémi Sándor, Anna Erdei, Zsuzsa Nagybalo, Zsuzsa Bajtay
    Abstract:

    CR3 and CR4 belong to the family of β2-integrins and play an important role in phagocytosis, cellular adherence and migration. CR3 and CR4 are generally expected to mediate similar functions due to their structural homology, overlapping ligand specificity and parallel expression on human phagocytes. Although the different signalling pathways of these receptors suggest distinct functions, possible differences are just being revealed. Previously we proved that CR3 plays a key role in the uptake of iC3b-opsonized particles by human dendritic cells. Now, besides measuring the overall phagocytic capacity of cells including the assessment of surface bound as well as internalized particles, we extended our investigations and studied the digestion of the iC3b opsonized antigen by various human phagocytes. The participation of CR3 and CR4 was compared in the process of binding, internalization and digestion of iC3b opsonized Staphylococcus aureus by monocytes, monocyte derived macrophages (MDMs), monocyte derived dendritic cells (MDDCs), and neutrophils. Comparing the activity of the two β2-integrin type complement receptors we found that CR3 plays a dominant role in the phagocytosis of iC3b opsonized S. aureus by all of these cell types. Studying another important integrin-mediated function we demonstrated earlier that CR4 is dominant in the adhesion of monocytes, MDMs and MDDCs to fibrinogen. Here we studied the participation of CR3 and CR4 in podosome formation by human phagocytes, since these structures are known to play an essential role in cell migration. Our confocal microscopy analysis revealed that both CD11b and CD11c concentrate in the podosome adhesion ring. In summary our data highlight differences in the function of human CR3 and CR4 in the process of uptake and digestion of complement opsonized antigen, while in the process of podosome formation, connected to cellular motility, both receptors equally take part.

  • CD11c cd18 dominates adhesion of human monocytes macrophages and dendritic cells over CD11b cd18
    PLOS ONE, 2016
    Co-Authors: Noémi Sándor, Szilvia Lukácsi, Norbert Orgovan, Bálint Szabó, Robert Horvath, Anna Erdei, Rita Ungaisalanki, Zsuzsa Bajtay
    Abstract:

    Complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) belong to the family of beta2 integrins and are expressed mainly by myeloid cell types in humans. Previously, we proved that CR3 rather than CR4 plays a key role in phagocytosis. Here we analysed how CD11b and CD11c participate in cell adhesion to fibrinogen, a common ligand of CR3 and CR4, employing human monocytes, monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells (MDDCs) highly expressing CD11b as well as CD11c. We determined the exact numbers of CD11b and CD11c on these cell types by a bead-based technique, and found that the ratio of CD11b/CD11c is 1.2 for MDDCs, 1.7 for MDMs and 7.1 for monocytes, suggesting that the function of CD11c is preponderant in MDDCs and less pronounced in monocytes. Applying state-of-the-art biophysical techniques, we proved that cellular adherence to fibrinogen is dominated by CD11c. Furthermore, we found that blocking CD11b significantly enhances the attachment of MDDCs and MDMs to fibrinogen, demonstrating a competition between CD11b and CD11c for this ligand. On the basis of the cell surface receptor numbers and the measured adhesion strength we set up a model, which explains the different behavior of the three cell types.