10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      CD11c/CD18 Dominates Adhesion of Human Monocytes, Macrophages and Dendritic Cells over CD11b/CD18

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references49

          • Record: found
          • Abstract: found
          • Article: not found

          Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability.

          Two methods to generate human dendritic cells from hematopoietic precursor cells in peripheral blood have recently been published. One approach utilizes the rare CD34+ precursors and GM-CSF plus TNF-alpha. The other method makes use of the more abundant CD34- precursor population and GM-CSF plus IL-4. Here we report a method that is based on the latter approach. However, the GM-CSF and IL-4 treated cells are not stable mature dendritic cells, e.g., the characteristic morphology and nonadherence of dendritic cells is lost if the cytokines are removed. We describe the need for a monocyte-conditioned medium to generate fully mature and stable dendritic cells. This is achieved by adding a 3 day 'maturation culture' to the initial 6-7 day culture in the presence of GM-CSF and IL-4. Macrophage-conditioned medium contains the critical maturation factors. Mature dendritic cells are defined by their pronounced display of motile cytoplasmic processes ('veils'), their high capacity to induce proliferative responses in resting T cells, particularly in naive umbilical cord T cells, their down-regulated antigen processing ability, and their characteristic phenotype: expression of CD83, high levels of MHC molecules and CD86, lack of CD115 and perinuclear dot-like CD68 staining. These features are stable for at least 3 days upon withdrawal of cytokines and conditioned media. IL-4 can be replaced by IL-13. When CD34+ progenitors are depleted from blood, there is only a minor reduction in the yield of dendritic cells by this method. We have adapted the method to consider several variables that are pertinent to clinical use, including a change from fetal calf serum to human plasma and to media approved for clinical use like X-VIVO or AIM-V. 1% plasma and RPMI 1640 are currently optimal. Additional reagents used for cell culture (Ig. cytokines) and cell separation (immunomagnetic beads) are approved for or already used in clinical applications. For 40 ml blood, the yield is 0.8-3.3 x 10(6) mature dendritic cells as defined by the expression of the new dendritic cell-restricted marker CD83. CD83+ cells constitute between 30 and 80% of all cells recovered at the end of the culture period. Yields can be enhanced up to six-fold if the blood donors are pretreated with G-CSF. Stable, mature dendritic cells generated by this method should be a powerful tool for active immunotherapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Syk is required for integrin signaling in neutrophils.

            The Syk tyrosine kinase plays a critical role in the signaling machinery of various receptors of the adaptive immune system. Here we show that Syk is also an essential component of integrin signaling in neutrophils. syk(-/-) neutrophils failed to undergo respiratory burst, degranulation, or spreading in response to proinflammatory stimuli while adherent to immobilized integrin ligands or when stimulated by direct crosslinking of integrins. Signaling from the beta(1), beta(2), or beta(3) integrins was defective in syk(-/-) cells. Syk colocalized with CD18 during cell spreading and initiated downstream signaling events leading to actin polymerization. Surprisingly, these defects in integrin-mediated activation did not impair the integrin-dependent in vitro or in vivo migration of syk(-/-) neutrophils or of cells deficient in Src-family kinases. Thus, integrins use different signaling mechanisms to support migration and adherent activation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Integrins and cell proliferation: regulation of cyclin-dependent kinases via cytoplasmic signaling pathways.

              Cell cycle progression in mammalian cells is strictly regulated by both integrin-mediated adhesion to the extracellular matrix and by binding of growth factors to their receptors. This regulation is mediated by G1 phase cyclin-dependent kinases (CDKs), which are downstream of signaling pathways under the integrated control of both integrins and growth factor receptors. Recent advances demonstrate a surprisingly diverse array of integrin-dependent signals that are channeled into the regulation of the G1 phase CDKs. Regulation of cyclin D1 by the ERK pathway may provide a paradigm for understanding how cell adhesion can determine cell cycle progression.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 September 2016
                2016
                : 11
                : 9
                : e0163120
                Affiliations
                [1 ]MTA-ELTE Immunology Research Group, Hungarian Academy of Sciences, Budapest, Hungary
                [2 ]Department of Immunology, Institute of Biology, Faculty of Science, Eötvös Loránd University, Budapest, Hungary
                [3 ]Department of Biological Physics, Institute of Physics, Faculty of Science, Eötvös Loránd University, Budapest, Hungary
                [4 ]Nanobiosensorics “Lendület” Group, Institute of Technical Physics and Material Sciences, Centre for Energy Research, Hungarian Academy of Sciences, Budapest, Hungary
                Singapore Immunology Network, SINGAPORE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: ZB AE RH.

                • Data curation: NS SL ZB AE.

                • Funding acquisition: ZB AE.

                • Methodology: NS SL RUS NO.

                • Project administration: ZB AE NS.

                • Resources: ZB AE.

                • Software: SL BS RH.

                • Visualization: NS SL RUS NO.

                • Writing – original draft: NS SL ZB AE.

                • Writing – review & editing: NS SL ZB AE.

                Author information
                http://orcid.org/0000-0002-2461-1389
                Article
                PONE-D-16-18895
                10.1371/journal.pone.0163120
                5033469
                27658051
                79c47a47-cecf-4cf6-b4d7-30c23229585c
                © 2016 Sándor et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 May 2016
                : 3 September 2016
                Page count
                Figures: 5, Tables: 0, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003549, Országos Tudományos Kutatási Alapprogramok;
                Award ID: 104838
                Award Recipient :
                Funded by: Magyar Tudományos Akadémia (HU)
                Award ID: MedInProt
                Award Recipient :
                Funded by: Magyar Tudományos Akadémia (HU)
                Award ID: MedInProt
                Award Recipient :
                Funded by: Magyar Tudományos Akadémia (HU)
                Award ID: Bolyai Scholarship
                Award Recipient :
                Funded by: Magyar Tudományos Akadémia (HU)
                Award ID: Lendület Program
                Award Recipient :
                Financial support from Hungarian Science Fund OTKA (Országos Tudományos Kutatási Alapprogramok) grant no. 104838 and Lendület (Momentum) Program of the Hungarian Academy of Sciences is gratefully acknowledged. The Bolyai Scholarship for BS and MedinProt grant for NS and BS from the Hungarian Academy of Sciences are greatly appreciated.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                White Blood Cells
                Monocytes
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                White Blood Cells
                Monocytes
                Biology and Life Sciences
                Immunology
                Immune Cells
                White Blood Cells
                Monocytes
                Medicine and Health Sciences
                Immunology
                Immune Cells
                White Blood Cells
                Monocytes
                Biology and Life Sciences
                Biochemistry
                Glycobiology
                Glycoproteins
                Fibrinogen
                Biology and Life Sciences
                Cell Biology
                Cell Adhesion
                Integrins
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Extracellular Matrix
                Integrins
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                White Blood Cells
                Macrophages
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                White Blood Cells
                Macrophages
                Biology and Life Sciences
                Immunology
                Immune Cells
                White Blood Cells
                Macrophages
                Medicine and Health Sciences
                Immunology
                Immune Cells
                White Blood Cells
                Macrophages
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                Antigen-Presenting Cells
                Dendritic Cells
                Biology and Life Sciences
                Immunology
                Immune Cells
                Antigen-Presenting Cells
                Dendritic Cells
                Medicine and Health Sciences
                Immunology
                Immune Cells
                Antigen-Presenting Cells
                Dendritic Cells
                Research and Analysis Methods
                Spectrum Analysis Techniques
                Spectrophotometry
                Cytophotometry
                Flow Cytometry
                Biology and life sciences
                Genetics
                Gene expression
                Gene regulation
                Small interfering RNAs
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Non-coding RNA
                Small interfering RNAs
                Research and Analysis Methods
                Specimen Preparation and Treatment
                Staining
                Cell Staining
                Custom metadata
                All relevant data are within the paper.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article