Progress in Clinical and Biological Research,vol.195
21,454 s.,obr.,tab.,grafy. : Bibliogr.,rejstřík.
Environmental health perspectives, ISSN 0091-6765 Supplement Vol. 106. 5
1119-1258 s. : il. ; 30 cm
Makrofágy představují stěžejní bod vzájemné interakce mezi patogenem a hostitelským organismem. Jsou nejen častou bránou vstupu invadujícího infekčního agens, zejména nitrobuněčných parazitů, ale zárověň i kompartmentem jejich pomnožení a další diseminace infekce. Francisella tularensis je modelovým nitrobuněčným patogenem způsobujícím granulomatózní procesy, jejichž klinická manifestace závisí na bráně vstupu. Osud F. tularensis uvnitř makrofágů a patogeneze vzniku onemocnění nejsou bezezbytku popsány. Našim cílem bylo vytvoření funkčního modelu infekce makrofágů myší monocyto-makrofágové linie J774.2 vakcinačním kmenem F. tularensis LVA za přesně definovaných podmínek jejich stimulace LPS a IFNy in vitro s ohledem na definici faktorů vzájemné interakce a přispění k popisu imunopatogeneze infekce. Infikované buňky byly amalyzovány mikroskopicky a průtokovou cytometrií, byla měřena produkce NO a vybraných cytokinů v supernatantu. Přežívání bakterie bylo hodnoceno pomocí CFU (Colony Forming Units). V pravidelných časových intervalech byly průtokovou cytometríí hodnoceny povrchové denzity molekul CD16/32 (FcyIII/IIR), CD54 (ICAM-1) a CD86 (B7.2) vyjádřené intenzitou fluorescence a hodnocené indexem MFI (Mean Fluorescence Index). Výsledky naší práce podporují hypotézu, že klíčovým faktorem imunopatogeneze infekce F. tularensis je inhibice stimulace infikované buňky. Vytvořený model aktivace makrofágů je univerzální a využitelný pro studium vlivu dalších nox na makrofágy, a to nejen infekčních.
Macrophages represent a key point of host-pathogen mutual interaction. They are not only a frequent gate for invading microbes especially intra- cellular parasites, but compartment of their replication as well. Francisella tularensis is a prototypical intracellular parasite causing granulomatous diseases. Their clinical significance is dependent on the course of invasion. The fate of F. tularensis inside the host cell, and the pathogenesis of the disease remain unclear. Our aim was to create a functional model of mouse monocyte-macrophage cell line J774.2 infected by F. tularensis LVS strain in defined conditions of lipopolysaccharide (LPS) and interferon gamma (IFNγ) in vitro stimulation with respect to mutual factors of interaction definition, to add new informations to current paradigma of F. tularensis infection. Infected cells were harvested and analysed by microscopy and by flow cytometry and likewise the NO and cytokines production was measured in cell supernatant. A survival of b acteria was assessed by colony forming units (CFU) count. The changes in the surface density of selected molecules (CD16/32 (FcγIII/IIR), C D54 (ICAM-1) and CD86 (B7.2)) expressed by changes in mean fluorescence index (MFI) in regular intervals were measured. Results of our work support the hypothesis, that F. tularensis infection can manipulate with signaling pathways of macr ophage to escape the immunosurveillance and to exploite intracellular compartment for hidden multiplic ation. Functional model of macrophages in vitro infection and stimulation seems to be universal and usefull tool for study of influence of various noxious factors on macrophages.
237 listů : ilustrace ; 30 cm
Dizertační práce, která se zaměřila na výzkum tularemie pomocí modelu buněčné imunitní reakce.
- MeSH
- Immunity, Cellular MeSH
- Models, Immunological MeSH
- Tularemia MeSH
- Publication type
- Academic Dissertation MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- alergologie a imunologie
- experimentální medicína
- infekční lékařství
Oscillating polar entities inside the biological cells, most notably microtubules, are bound to emit electromagnetic radiation. This phenomenon is described by Fröhlich kinetic equations expressing, in terms of quantum occupancy numbers of each discrete collective oscillatory mode, the balance between incoming metabolic energy flow and losses due to linear and non-linear interactions with the thermal environs of the oscillators. Hitherto, radiation losses have not been introduced as part of the balance; it was assumed that they were proportional to the modal occupation numbers. It is demonstrated that this formulation is incorrect and the radiation losses must be taken into account in the kinetic equations explicitly. Results of a numerical study of kinetic equations, enlarged in this sense, are presented for the case of three coupled oscillators which was shown to evince the essential attributes of the Fröhlich systems. Oscillator eigenfrequencies were chosen, alternatively, to fall into the MHz and the THz frequency domains. It was found that large radiation levels destroy the main hallmark of the Fröhlich systems, the energy condensation in the lowest frequency mode. The system then functions as a convertor of metabolic energy into radiation. At more moderate radiation levels, both energy condensation and significant radiation can coexist. Possible consequences for the cell physiology are suggested.
- MeSH
- Adenosine Triphosphate chemistry MeSH
- Models, Biological MeSH
- Cell Membrane metabolism MeSH
- Cytoskeleton radiation effects MeSH
- Electromagnetic Radiation * MeSH
- Guanosine Triphosphate chemistry MeSH
- Kinetics MeSH
- Oscillometry MeSH
- Elasticity MeSH
- Thermodynamics MeSH
- Publication type
- Journal Article MeSH
Fröhlich model describes emission of electromagnetic field in the interior of biological cells by oscillating polar units, now mostly identified with microtubule filaments. Central element of this theory is the system of rate equations for the quantum occupancy numbers n i of collective oscillation modes. These equations describe both linear and nonlinear properties of the system; presence of the latter can lead to condensation of the incoming energy into the lowest frequency mode - a phenomenon deemed to be of major importance for cell's biochemistry, because the excited mode can engage in chemical reactions while the major part of the system remains near the equilibrium, not exposed to energetic stress. This paper explores, using a simple model, the influence of strong static electric field created by mitochondria flanking the microtubules on nonlinear interactions and, in turn, on occupancy numbers. The computed results show that simultaneous presence of both sufficient metabolic pumping and adequately elevated static electric field is necessary for the full unfolding of the hallmark properties of the Fröhlich model. It is suggested that cancer-related mitochondrial dysfunction leading to metabolic transformation has additional adverse effect mediated by diminution of static fields which in turn reduces the nonlinear processes in the Fröhlich systems, essential for energy condensation in the fundamental mode.
