Blog
About

0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Methods for Testing Immunological Factors

      Drug Discovery and Evaluation: Pharmacological Assays

      Read this article at

      ScienceOpenPublisherPMC
      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

          Hypersensitivity reactions can be elicited by various factors: either immunologically induced, i.e., allergic reactions to natural or synthetic compounds mediated by IgE, or non-immunologically induced, i.e., activation of mediator release from cells through direct contact, without the induction of, or the mediation through immune responses. Mediators responsible for hypersensitivity reactions are released from mast cells. An important preformed mediator of allergic reactions found in these cells is histamine. Specific allergens or the calcium ionophore 48/80 induce release of histamine from mast cells. The histamine concentration can be determined with the o-phthalaldehyde reaction.

          Related collections

          Most cited references 686

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

          Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1.

          Adaptive immunity depends on T-cell exit from the thymus and T and B cells travelling between secondary lymphoid organs to survey for antigens. After activation in lymphoid organs, T cells must again return to circulation to reach sites of infection; however, the mechanisms regulating lymphoid organ exit are unknown. An immunosuppressant drug, FTY720, inhibits lymphocyte emigration from lymphoid organs, and phosphorylated FTY720 binds and activates four of the five known sphingosine-1-phosphate (S1P) receptors. However, the role of S1P receptors in normal immune cell trafficking is unclear. Here we show that in mice whose haematopoietic cells lack a single S1P receptor (S1P1; also known as Edg1) there are no T cells in the periphery because mature T cells are unable to exit the thymus. Although B cells are present in peripheral lymphoid organs, they are severely deficient in blood and lymph. Adoptive cell transfer experiments establish an intrinsic requirement for S1P1 in T and B cells for lymphoid organ egress. Furthermore, S1P1-dependent chemotactic responsiveness is strongly upregulated in T-cell development before exit from the thymus, whereas S1P1 is downregulated during peripheral lymphocyte activation, and this is associated with retention in lymphoid organs. We find that FTY720 treatment downregulates S1P1, creating a temporary pharmacological S1P1-null state in lymphocytes, providing an explanation for the mechanism of FTY720-induced lymphocyte sequestration. These findings establish that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand.

            Bone remodelling and bone loss are controlled by a balance between the tumour necrosis factor family molecule osteoprotegerin ligand (OPGL) and its decoy receptor osteoprotegerin (OPG). In addition, OPGL regulates lymph node organogenesis, lymphocyte development and interactions between T cells and dendritic cells in the immune system. The OPGL receptor, RANK, is expressed on chondrocytes, osteoclast precursors and mature osteoclasts. OPGL expression in T cells is induced by antigen receptor engagement, which suggests that activated T cells may influence bone metabolism through OPGL and RANK. Here we report that activated T cells can directly trigger osteoclastogenesis through OPGL. Systemic activation of T cells in vivo leads to an OPGL-mediated increase in osteoclastogenesis and bone loss. In a T-cell-dependent model of rat adjuvant arthritis characterized by severe joint inflammation, bone and cartilage destruction and crippling, blocking of OPGL through osteoprotegerin treatment at the onset of disease prevents bone and cartilage destruction but not inflammation. These results show that both systemic and local T-cell activation can lead to OPGL production and subsequent bone loss, and they provide a novel paradigm for T cells as regulators of bone physiology.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists.

              Blood lymphocyte numbers, essential for the development of efficient immune responses, are maintained by recirculation through secondary lymphoid organs. We show that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolite of the immunosuppressive agent FTY720. Both species were high-affinity agonists of at least four of the five S1P receptors. These agonists produce lymphopenia in blood and thoracic duct lymph by sequestration of lymphocytes in lymph nodes, but not spleen. S1P receptor agonists induced emptying of lymphoid sinuses by retention of lymphocytes on the abluminal side of sinus-lining endothelium and inhibition of egress into lymph. Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression.
                Bookmark

                Author and article information

                Contributors
                +4949+ 49 (0)6071 98 05 06 , dr.fjhock@t-online.de
                martin.braddock@astrazeneca.com
                Journal
                978-3-319-05392-9
                10.1007/978-3-319-05392-9
                Drug Discovery and Evaluation: Pharmacological Assays
                Drug Discovery and Evaluation: Pharmacological Assays
                978-3-319-05391-2
                978-3-319-05392-9
                28 July 2015
                : 2091-2203
                Affiliations
                CorDynamics, Dieburg, Germany
                Global Medicines Development Respiratory Projects, AstraZeneca R&D, Alderley Park, Cheshire, SK10 4TG Cheshire, England UK
                Article
                45
                10.1007/978-3-319-05392-9_45
                7122208
                © Crown Copyright 2016

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                Categories
                Article
                Custom metadata
                © Springer International Publishing Switzerland 2016

                Comments

                Comment on this article