ABSTRACT
BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis (HP) are immunologically mediated processes caused by hypersensitivity reaction accompanied by similar features including lymphocytic alveolitis and granuloma formation. Recent studies describe the role of TREM receptors in T cell activation, differentiation, and granuloma formation. Alveolar macrophages activation via TREM receptors may be the key factor mediating subsequent immune response. The aim of the study was to analyse TREM-1 and TREM-2 expression to identify further molecular mechanisms participating in the immunopathogenesis of sarcoidosis and HP. METHODS: Flow cytometry was performed to analyse TREM-1 and TREM-2 expression on CD14+ cells in bronchoalveolar lavage fluid from patients having sarcoidosis or HP and a control group. RESULTS: The study proved increased TREM-1 expression on alveolar macrophages in pulmonary sarcoidosis and diminished TREM-1 expression in HP-Sarcoidosis: median: 76.7; HP: median: 29.9; control: median: 53.3, (sarcoidosis versus HP: p < 0.001; sarcoidosis versus control: p < 0.05). TREM-2 expression was increased in both, sarcoidosis and HP-sarcoidosis: median: 34.79; HP: median: 36.00; control: median: 12.98, (sarcoidosis versus control: p < 0.05; HP versus control: p < 0.05). Correlation analysis showed negative correlation between TREM-1 and total number of CD8+ cytotoxic T cells. In sarcoidosis TREM-1 expression decreased with changes of HRCT image, decrease in CD4/CD8 ratio and decrease in DLCO. CONCLUSIONS: Differences in TREM receptor expression in sarcoidosis (increase in TREM-1 and TREM-2) and HP (increase in TREM-2) and correlation analysis suggests that activation via TREM may participate in typical immunological characteristics of sarcoidosis and HP.
Subject(s)
Bronchoalveolar Lavage Fluid , Lipopolysaccharide Receptors/metabolism , Membrane Glycoproteins/metabolism , Receptors, Immunologic/metabolism , Sarcoidosis, Pulmonary/metabolism , T-Lymphocytes/immunology , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Adult , Aged , Brain Neoplasms/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Glioma/metabolism , Humans , Immune System , Inflammation , Interleukin-10/metabolism , Interleukin-6/metabolism , Male , Middle Aged , Monocytes/metabolism , Proportional Hazards ModelsABSTRACT
The production of certified reference materials requires the application of highly accurate methods for characterisation. A gas chromatography-isotope dilution mass spectrometry method, setting ambitious performance criteria, was developed for eight selected pesticides in soybeans. Pressurised liquid extraction was followed by automated gel-permeation chromatography and solid-phase extraction clean-up. Pesticides identification respected a Commission Decision and guidelines of the Directorate General for Health and Food Safety (DG SANTE). Reliable quantification involved stable isotopically labelled analogues as internal standards. Validation, according to ISO/IEC 17,025 and DG SANTE guidelines, assessed linearity, LOD/LOQ, trueness, selectivity, precision, stability and robustness. Mean recoveries ranges (83-109%, relative standard deviations < 3%), repeatability (2.2-4.8%), day-to-day variation (0.6-4.2%) and combined uncertainty (1.2-4.2%) were fit for purpose. The method is highly accurate and suitable for certification of the selected pesticides in soybean matrix reference material. Chemical compounds studied in this article: Diazinon (PubChem CID: 3017); malathion (PubChem CID: 4004); chlorpyrifos (PubChem CID: 2730); captan (PubChem CID: 8606); endosulfan (PubChem CID: 3224); tebuconazole (PubChem CID: 86,102); iprodione (PubChem CID: 37,517); cypermethrin (PubChem CID: 2912).
Subject(s)
Glycine max/chemistry , Pesticides/analysis , Gas Chromatography-Mass Spectrometry , Indicator Dilution TechniquesABSTRACT
The innate immune system senses invading microorganisms by a phylogenetically conserved family of proteins PRRs of which TLRs are ones of the most important. There are at least 10 different TLRs in humans and 11 in mice. They have in the course of evolution specialized for the recognition of conserved structures among microorganisms called PAMPs. Activation of TLRs results in induction of innate immunity mechanisms as well in development of antigen-specific adaptive immune responses, thus bridging innate and adaptive immunity.
Subject(s)
Ligands , Toll-Like Receptors/chemistry , Animals , Humans , Immunity, Innate , Intracellular Signaling Peptides and Proteins , Mice , Models, Biological , Signal Transduction , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/immunology , Toll-Like Receptor 4/metabolism , Toll-Like Receptors/metabolism , Toll-Like Receptors/physiologyABSTRACT
The innate immune system senses invading microorganisms by a phylogenetically conserved family of proteins--TLRs. They are expressed in several types of cells that represent a route of entry of pathogens into the host organism and that can contribute to protection against infection. Except for cells of the immune system, TLRs are present in epithelial cells of the skin, respiratory, intestinal, and genitourinary tracts that form the first protective barrier to invading pathogens. Polarized regulation of TLR expression in epithelial cells explains why pathogenic but not commensal bacteria elicit inflammatory responses. TLR-induced intracellular signalling pathways show remarkable complexity: apart from a common signalling pathway, additional signalling pathways specific for each of the TLRs are responsible for a fine tuning of the immune response, thus securing effective pathogen-directed biological responses.
Subject(s)
Adaptor Proteins, Signal Transducing/physiology , Toll-Like Receptors/physiology , Transcription Factors/physiology , Humans , Ligands , Models, BiologicalABSTRACT
The ability of the innate immune system to recognize and respond to microbial components has been largely attributed to the family of TLRs. They are able to discriminate among distinct molecular patterns associated with microbial components. Recognition of microbial products by TLRs results in induction of innate immunity mechanisms as well in development of antigen-specific adaptive immune responses. Some of TLR ligands start to be used to enhance immune defence mechanisms in fighting infections or malignancies. On the contrary, others were shown to be involved in immunopathogenesis of autoimmune disorders such as SLE.
Subject(s)
Toll-Like Receptors/physiology , Autoimmunity , Defensins/immunology , Humans , Immunity, Innate , Intracellular Signaling Peptides and Proteins/physiology , Signal Transduction , alpha-DefensinsABSTRACT
(1) The failure of ;Slow-K' tablets to disintegrate prevents rapid release but allows them to be trapped by their bulk in the intestine.(2) Two cases are reported. In the first the tablet was trapped in a caecal diverticulum and the patient developed an abcess. In the second, abdominal pain developed which subsided when ;Slow-K' was stopped. Later ;Slow-K' was again started and the patient developed dysphagia.(3) The possibility of abdominal complications with this treatment should be remembered.(4) Effervescent KC1 preparations may replace ;Slow-K' but KC1 supplementation may be necessary only in cardiac disease.
