Studies of the role of macrophages in phagocytosis are of great theoretical and practical importance for understanding how these cells are involved in the organism's defense response and in the development of various pathologies. Here we investigated phagocytic plasticity of THP-1 (acute monocytic human leukemia) cells at different stages (days 1, 3, and 7) of phorbol ester (PMA)-induced macrophage differentiation. Analysis of cytokine profiles showed that PMA at a concentration of 100 nM induced development of the proinflammatory macrophage population. The functional activity of macrophages was assessed on days 3 and 7 of differentiation using unlabeled latex beads and latex beads conjugated with ligands (gelatin, mannan, and IgG Fc fragment) that bind to the corresponding specific receptors. The general phagocytic activity increased significantly (1.5-2.0-fold) in the course of differentiation; phagocytosis occurred mostly through the Fc receptors, as shown previously for M1 macrophages. On day 7, the levels of phagocytosis of gelatin- and Fc-covered beads were high; however, the intensity of ingestion of mannan-conjugated beads via mannose receptors increased 2.5-3.0-fold as well, which indicated formation of cells with an alternative phenotype similar to that of M2 macrophages. Thus, the type and the plasticity of phagocytic activity at certain stages of macrophage differentiation can be associated with the formation of functionally mature morphological phenotype. This allows macrophages to exhibit their phagocytic potential in response to specific ligands. These data are of fundamental importance and can be used to develop therapeutic methods for correcting the M1/M2 macrophage ratio in an organism.
Некротизирующий саркоидный гранулематоз (НСГ) -продуктивный васкулит мелких артерий и вен с образова-нием массивных скоплений саркоидоподобных гранулем, сопровождающийся ишемическим некрозом разной сте-пени выраженности и давности. Заболевание поражает исключительно легкие. Этиология и патогенез НСГ оста-ются малоизученными из-за редкого выявления этого за-болевания, отсутствия патогномоничных лабораторных, лучевых и функциональных критериев. Согласно мирово-му опыту, основным методом диагностики НСГ остается морфологическое исследование [1][2][3][4].Термин «некротизирующий саркоидный гранулема-тоз» был впервые предложен в 1973 г. А. Liebov [5]. Автор описал 11 наблюдений пациентов, в биоптатах легких ко-торых гистологически был выявлен продуктивный васку-лит. Васкулит сопровождался наличием саркоидоподоб-ных гранулем с образованием конгломератов и некроти-ческими изменениями. При этом отсутствовала внутри-грудная лимфаденопатия, характерная для саркоидоза. У этих пациентов наступала регрессия процесса спонтан-но или после непродолжительной терапии. necrotizing sarcoid granulomatosis (nsG) belongs to productive small-vessel vasculitis with the formation of sarcoid-like granulomas, which is accompanied by ischemic necrosis of varying degrees and duration. The disease involves the lung only. The clinical symptoms of the disease are nonspecific so the latter is detected rather rarely. The main diagnostic technique is morphological examination. Immune complex inflammation develops in the vessel walls with the formation of macrophage-histiocytic granulomas that do not contain epithelioid cells. The etiology and pathogenesis of nsG remain little studied. Its differential diagnosis is mainly presented with tuberculosis, sarcoidosis, and granulomatosis with polyangiitis.
One of the key requirements for the diagnosis of pulmonary tuberculosis is the identification of M. tuberculosis in tissue. In this paper, we present the advantages of specific fluorescent antibody labelling, combined with laser scanning confocal microscopy (LSCM), for the detection of M. tuberculosis in histological specimens of lung tissues. We demonstrate that the application of LSCM allows: (i) The automatic acquisition of images of the whole slice and, hence, the determination of regions for subsequent analysis; (ii) the acquisition of images of thick (20–40 μm) slices at high resolution; (iii) single bacteria identification; and (iv) 3D reconstruction, in order to obtain additional information about the distribution, size, and morphology of solitary M. tuberculosis; as well as their aggregates and colonies, in various regions of tuberculosis inflammation. LSCM allows for the discrimination of the non-specific fluorescence of bacteria-like particles and their aggregates presented in histological lung samples, from the specific fluorescence of labelled M. tuberculosis, using spectrum emission analysis. The applied method was effective in the identification of M. tuberculosis in lung histological samples with weak Ziehl–Neelsen staining. Altogether, combining immunofluorescent labelling with the application of LSCM visualization significantly increases the effectiveness of M. tuberculosis detection.
Interstitial changes in the lungs could be caused by vast majority of diseases including tuberculosis, sarcoidosis, hypersensitive pneumonitis, metastatic injury of the lungs, etc. Differential diagnosis of pulmonary dissemination remains an urgent and challenging clinical task. This article is a review of published literature and presentation of a clinical case of a patient with interstitial lung disease. The case demonstrates diagnostic difficulties in identification the cause of interstitial lung injuries. Interstitial lung injury was incidentally found in this patient and initially was considered as disseminated pulmonary tuberculosis. In-depth diagnostic work-up including lung tissue biopsy allowed diagnosis of lymphoid interstitial pneumonia associated with common variable immune deficiency. This case demonstrates common misdiagnosis of pulmonary tuberculosis in a patient with interstitial lung injury.
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