ABSTRACT
The purpose of the present review was to analyze the accumulating evidence regarding recently discovered novel defense mechanism of neutrophils - capacity to form neutrophil extracellular traps (NETs). Contact with pathogenic microbes and/or exposure to proinflammatory cytokines trigger the respiratory burst in the neutrophils with a subsequent initiation of a cell death (NETosis) which differs from apoptosis and necrosis. NETs are formed by the fibrils of decondensed chromatin (DNA/ histones), released from the neutrophil, which is closely associated with the antimicrobial proteins of cytoplasmic granules. Due to its three-dimensional structure, NETs are capable of retaining the microorganisms (bacteria, fungi and protozoa), while high local concentration of the antimicrobial substances provides their killing. The review presents the evidence of a potential defensive role of NETs in infectious diseases, traumas and surgical operations, as well as during the early stage of a repair process. Considering the role played by neutrophils in the immune response orientation via pentraxin-3 (PTX3), including the switching to adaptive immunity, it is necessary to study the subsequent interaction of DNA/histone exrtacellular structures with the tissue microenvironment.
Subject(s)
Morphogenesis , Neutrophils , Cell Death , Extracellular Space/immunology , Humans , Immunity, Innate , Neutrophils/immunology , Neutrophils/pathology , Neutrophils/physiology , Phagocytosis/immunology , Phagocytosis/physiologyABSTRACT
This review paper describes the evolution of the ideas of periodontal tissue regeneration, starting with the concept of selective cellular repopulation, stimulation of resident precursor cells in the regeneration focus, up to the application of versatile potential of the stromal stem cells (SSC). Effects of stem cells isolated from an embryo, bone marrow, and adipose tissue, are described, as well as the immunophenotype of freshly isolated SSC, that of precultured vascular cell fraction as compared with the immunophenotype of SSC cultured during various time periods. The results of the study of the processes of proliferation and cell differentiation of SSC transplanted into the deep periodontal defects, are analyzed using proliferating cell nuclear antigen (PCNA) and green fluorescent protein. During the process of regeneration, the interaction of transplanted SSC with the local microenvironment is mediated by special membranous cell receptors. The coordination of cell behavior by means of adhesive and communicative contacts which provide a signal platform for the control of cellular functions, is discussed.
Subject(s)
Alveolar Bone Loss/surgery , Bone Regeneration/physiology , Stem Cell Transplantation , Stromal Cells/transplantation , Alveolar Bone Loss/pathology , Animals , Cell Differentiation/physiology , HumansABSTRACT
The paper gives new information on the molecular mechanisms of pathogen reception in the human organism. The leading role is ascribed to the toll-like receptors recognizing the molecular structures of pathogens for bringing into operation natural resistance reactions with activation of transcription factors. Transmembrane TLRs are expressed on macrophages, dendritic, epithelial and other cells, calling for transmission of a signal of the presence of some adapter proteins. The considered effects of Porphycomonas gingivalis, the key periodontal pathogen, favor the chronic pattern of an inflammatory-destructive process due to its persistence in tissues, by inducing the expression of TLRs. It is suggested that recovered periodontal tissues in the natural structure and function are able to inhibit the expression of TLRs and to produce immune activators.
Subject(s)
Periodontitis/metabolism , Periodontium/metabolism , Toll-Like Receptors/physiology , Bacteroidaceae Infections/metabolism , Bacteroidaceae Infections/microbiology , Cytokines/metabolism , Gingivitis/metabolism , Gingivitis/microbiology , Gingivitis/pathology , Humans , NF-kappa B/metabolism , Periodontitis/microbiology , Periodontitis/pathology , Periodontium/microbiology , Periodontium/pathology , Porphyromonas gingivalis/physiology , Signal TransductionABSTRACT
Gap junctions provide humoral and electric communication between the cells, thus contributing to their morpho-functional cooperation. Gap junction is formed by multiple intercellular channels, each of them being made by two closed hemichannels--connexons, that are oligomeric transmembrane proteins built by 6 subunits, belonging to connexin family. Permeability and electric conductivity of gap junction channels is determined by molecular peculiarities of connexins, their capacity for phosphorilation and by some extra- and intracellular factors. According to the current data, gap junctions in both cell cultures and tissues are dynamic structures with a short half-life period. Main mechanisms responsible for gap junction assembly and destruction have been discovered. These mechanisms were shown to depend upon peculiarities of differential genome activity and to be controlled by extra- and intracellular factors. The data on the gap junctions in the nervous system, heart and epidermis are presented.
Subject(s)
Cell Communication , Connexins/metabolism , Gap Junctions/metabolism , Animals , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Epidermis/metabolism , Epidermis/ultrastructure , Gap Junctions/physiology , Gap Junctions/ultrastructure , Humans , Myocardium/metabolism , Myocardium/ultrastructure , Nerve Tissue/metabolism , Nerve Tissue/ultrastructure , Organ SpecificityABSTRACT
Subarachnoidal hemorrhage (SAH) causes cerebrovascular endothelial dysfunction that leads to impaired nitrosidergic vasorelaxation, delayed vasospasm, and cerebral ischemia. The purpose of the present review is to study the current potentialities of drug action on the system of generation of and the functional activity of nitric oxide (NO) in order to prevent and treat cerebral ischemic complications due to SAH. A scheme of the biosynthesis of NO and the mechanism of nitroxidergic vasorelaxation is presented. According to the direction of the action of a pharmacological agent (the biochemical target), the authors identified six groups of methods: 1) regulation of the level of a substrate; 2) activation of inhibition of NO-synthase enzymes; 3) action on the level of cofactors; 4) that on the metabolism of endogenous NO; 5) administration of exogenous NO; 6) action of the effector system of NO/cGMF. They show that not always an individual method is shown to be rather effective and safe for the treatment of patients after SAH. A concept of the combined use of methods from different groups for the synergism and potentiation of their impact on nitroxidergic vasorelaxation with a minimum of adverse effects is proposed.
Subject(s)
Subarachnoid Hemorrhage/complications , Vasodilation/physiology , Vasospasm, Intracranial/drug therapy , Vasospasm, Intracranial/etiology , Arginine/pharmacology , Cyclic GMP/metabolism , Drug Design , Enzyme Inhibitors/pharmacology , Humans , Nitric Oxide/metabolism , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Subarachnoid Hemorrhage/physiopathology , Vasodilation/drug effectsSubject(s)
Bone Marrow Cells , Histology/history , Stem Cells , Animals , Connective Tissue Cells , Hematopoiesis , History, 19th Century , History, 20th Century , HumansABSTRACT
Preparation for labour and its induction are controlled by an integrative but not single process. The primary stimulus that comprises this integrative hormonal prostaglandin-leukocytic mechanism is a suppression of local progesterone action with further inhibition of perivascular prostaglandine dehydrogenase and sharp increase of E2 and F2 prostaglandine content in uteroplacentary mechanism bed. Vasodilatory effect of prostaglandines along with synergication of interleukine 8 leads to leukocyte emigration and formation of infiltrates consisting of neutrophilic granulocytes and certain number of macrophages and mast cells. Hydrolytic enzymes released by neutrophilic granulocytes cause degradation of collagenic tissue in uterine cervix promoting its ripening. The factors mentioned also influence loosening of choriodecidual interface. Further amplification of effect of prostaglandine including those produced by neutrophilic granulocytes along with the other uteroconstrictors increase myometrium contractions which leads to labour induction.
Subject(s)
Labor Onset/physiology , Labor, Obstetric/physiology , Leukocytes/physiology , Animals , Cervical Ripening/physiology , Dinoprost/physiology , Dinoprostone/physiology , Female , Humans , Interleukin-8/physiology , Pregnancy , Progesterone/physiologyABSTRACT
Subarachnoidal hemorrhage leads to impaired endothelium-dependent relaxation by inhibiting the synthesis of major vascular relaxation agent nitric oxide (NO). Nitrite, a closest product of the oxidation of NO, is responsible for the synthesis of the latter. The Griss reaction was used for daily measurement of blood nitrite levels in 32 patients with acute subarachnoidal hemorrhage of aneurysmal etiology. There were upward and downward changes in nitrite levels as compared to the levels of healthy individuals (0.26 +/- 0.06 mu/ml): the levels of nitrite were 1.5-3 times higher than the normal levels in the first 2 days after hemorrhage and its concentration was the minimum (less than 0.16 mu/ml) when there was the greatest likelihood of development of vascular spasm. There was an association of dynamic changes in nitrite levels with the course of the disease. If vascular spasm was absent, the concentration of nitrite returned to the normal range at week 2 of hemorrhage. When there was significant and permanent vascular spasm frequently leading to death, the levels of nitrite was constantly below the normal range.
Subject(s)
Nitrites/blood , Subarachnoid Hemorrhage/blood , Acute Disease , Adolescent , Adult , Aged , Aneurysm, Ruptured/blood , Aneurysm, Ruptured/complications , Biomarkers/blood , Child , Female , Humans , Intracranial Aneurysm/blood , Intracranial Aneurysm/complications , Male , Middle Aged , Severity of Illness Index , Subarachnoid Hemorrhage/etiology , Time FactorsABSTRACT
Signal sequences of inflammation and regeneration are presented. The number of factors such as sensor neuropeptides, lipid mediators, interleukins and factors of growth are shown to participate in the initiation and regulation of inflammation. These factors are produced in a certain sequence by various structures: cells-object of damage, opsonocytophagic and immune cells, connective tissue cells. This results in the stimulation of adhesion proteins, processes of migration, chemotaxis, interaction with components of the intercellular matrix and parenchyma cells of the viscera. Fibroblast is considered to be the central figure in the resolution of inflammation and its chronization. The regulation of the process occurs with the help of autocrine regulation and apoptosis of functionally exhausted cells.
Subject(s)
Inflammation Mediators , Regeneration/physiology , Apoptosis/physiology , Fibroblasts/physiology , Growth Substances/physiology , Humans , Interleukins/physiology , Lipids/physiology , Neuropeptides/physiologyABSTRACT
Chromatin anisotropy is measured and its correlation with the cytochemical activity of leukocytes estimated in 19 patients with icterohemorrhagic leptospirosis. Leukocyte and neutrophil nuclei chromatin anisotropy increases during the acute period of leptospirosis, indicating an increase of cuchromatization and transcription activity. Neutrophil nuclei euchromatization is observed in patients with all forms of leptospirosis irrespective of the disease severity. Lymphocyte nuclei euchromatization is observed only in the patients with a favorable course but not in those with the severe course of the disease. Correlations between neutrophil and lymphocyte nuclei euchromatization and cytochemical activity of lymphocytes and monocytes are detected. The optic anisotropic effect is proposed to be used as an extra diagnostic criterion of leptospirosis severity.
Subject(s)
Chromatin/ultrastructure , Leptospirosis/blood , Leukocytes/ultrastructure , Adult , Anisotropy , Chromatin/metabolism , Humans , Leptospirosis/genetics , Leptospirosis/pathology , Male , Middle AgedABSTRACT
The process of intercellular interactions during morphogenesis, inflammation and malignant growth are considered from the point of view of possible intercellular contacts provided by cell adhesion molecules. The system analysis of different cell adhesion molecules classes? their structure and influence on functional cell activity is performed. Clinical importance of expression disturbances of cell adhesion molecules at various pathological processes is considered.
Subject(s)
Cell Adhesion Molecules/physiology , Inflammation/physiopathology , Neoplasms/physiopathology , Cell Adhesion/physiology , Humans , Inflammation/pathology , Morphogenesis , Neoplasms/pathologyABSTRACT
Measurements of DNA and study of chromatin status in blood cell nuclei help solve numerous basic problems of biology and medicine. Acid lability of DNA was assessed in 5 patients with grave icterohemorrhagic leptospirosis. The distribution of fluorescence peaks on the curve of neutrophil DNA hydrolysis in patients with grave leptospirosis indicates that functionally low-active acid-resistant DNA fraction predominates in their chromatin. Assessment of acid lability of DNA is proposed to be used for assessing the severity of the pathological process.
Subject(s)
DNA/analysis , Weil Disease/diagnosis , Weil Disease/genetics , Acids , Adult , Aged , Cell Nucleus/ultrastructure , Chromatin/genetics , Female , Fluorescence , Humans , Hydrolysis , Male , Middle Aged , Neutrophils/cytologyABSTRACT
The values of spontaneous NBT test significantly rise at the peak of leptospirosis in patients with an uncomplicated course of the disease (p < 0.05). Low values of the spontaneous NBT test with stimulation with Staphylococcus in patients with grave leptospirosis predict the development of life-threatening complications. Leptospirosis vaccine reduced the elevated values of the NBT in leptospirosis. The depressing effect of leptospirosis vaccine is indicative of a high risk of development of late complications.
Subject(s)
Nitroblue Tetrazolium , Weil Disease/diagnosis , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , PrognosisABSTRACT
The condition of the cellular link of the immune system was studied in 30 patients with various forms of acute peritonitis. It was found that the reaction of the immune system in peritonitis is characterized by a phase property and is manifested by processes of redistribution and activation of the immunocompetent cells and normalization of reactivity. The ratio of these phases is determined by the severity of inflammation and intoxication. It is shown that inhibition of the immune system is most marked in diffuse peritonitis, which is due to the higher absorption capacity of the peritoneum in this stage of the pathological process. It was established that the response of the immune system to the operative trauma depends on the spread of peritonitis. The number of T-helpers, T-suppressors, and activated lymphocytes and the activity of the neutrophil alkaline phosphatase are most important in the prognosis of postoperative complications. These parameters may also be used in assessment of the efficacy of immunomodulation with levamisole.
Subject(s)
B-Lymphocytes/immunology , Intestinal Perforation/immunology , Neutrophils/immunology , Peritonitis/immunology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology , Acute Disease , Adolescent , Adult , Aged , Alkaline Phosphatase/blood , Appendicitis/complications , Combined Modality Therapy , Female , Humans , Intestinal Perforation/blood , Intestinal Perforation/drug therapy , Intestinal Perforation/surgery , Levamisole/therapeutic use , Lymphocyte Activation , Middle Aged , Peptic Ulcer Perforation/complications , Peritonitis/blood , Peritonitis/drug therapy , Peritonitis/surgery , Postoperative Complications/prevention & control , Prognosis , Rupture, Spontaneous , Stomach Ulcer/complicationsABSTRACT
Connections of the neurons of the spinal cord ventral horn with the structures, situating above have been investigated. After injection of uranyl acetate into the TIII segment of the spinal cord, labelled neurons are found in various reticular nuclei of the medulla oblongata. At the level of the roots of the XII pair of the cranial nerves they are revealed in the reticular paramedian, ventral, parvocellular and lateral nuclei. The formations mentioned participate in regulation of the cardio-vascular system. More rostral (2 and 4 mm relatively to the roots of the XII pair of the cranial nerves) the neurons are observed in the reticular giant cellular nucleus, in nuclei of the raphe and in the group of the P-substance reactive neurons. Besides, labelled neurons are revealed in the posterior, lateral fields and in the dorso- and ventromedial nuclei of the hypothalamus.