Plasticity of Human THP-1 Cell Phagocytic Activity during Macrophagic Differentiation.

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.

[Necrotizing sarcoid granulomatosis]. / Nekrotiziruyushchii sarkoidnyi granulematoz.

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.

In vitro effects of pulmonary surfactant on macrophage morphology and function.

The effects of pulmonary surfactant on the morphology and functioning of young macrophages were studied on the model of monocyte/macrophage differentiation in vitro and on macrophages of the bronchial alveolar lavage fluid. Surfactant is not a differentiation inductor, but it stimulated the maturation and phagocytic activity of young macrophages. The stimulatory effect of surfactant on phagocytic activity of macrophages persisted even after its removal from the culture medium.

[Complex morphological diagnostics of tuberculosis and sarcoidosis of the lungs].

Differential diagnosis of disseminated lung diseases, particularly tuberculosis and sarcoidosis, presents certain difficulties for clinicians. In the verification of the diagnosis a decisive role belongs to the morphological study, for which the most commonly used material is transbronchial biopsy. Diagnostic signs of active disseminated pulmonary tuberculosis are presence of different-sized granulomas with signs merger, necrosis, infiltration of polymorphonuclear leukocytes, weakly expressed fibrillogenesis. Cytological markers of a specific process are young biosinteziruyuschie macrophages and acid-fast bacilli. The diagnostic features of pulmonary sarcoidosis are monomorphic granulomas with no tendency to merge and necrotisation expressed fibrosis and hyalinization processes. Cytological marker for the disease is the high content of epithelioid cells with signs of secretion.

[Optimisation of diagnostics and differential diagnostics disseminated pulmonary tuberculosis].

One of the reasons of dramatic situation with tuberculosis in Russia is untimely diagnostics of tuberculosis. The aim of the study was to identify the causes of diagnostic mistakes when we deal with disseminated pulmonary tuberculosis at current stage and to modernize the diagnostic process. The analysis of the diagnostic activity of the consultative diagnostic center of Central Tuberculosis Research Institute of Russian Academy Medical Sciences for 2011 was performed with special attention on the results of the survey of 505 patients with pulmonary dissemination. The frequency of discrepancies of disseminated pulmonary tuberculosis diagnostics was 96.1%. Based on the studies carried out the main causes diagnostic mistakes in patients with disseminated pulmonary tuberculosis were determined. New directions of improving of tuberculosis diagnostics were developed: overall high-technology examination of patient, adherence to the diagnostic procedure, developed by consultative diagnostic center of Central Tuberculosis Research Institute (CTRI), timely performing fiber-optic bronchoscopy with complex biopsy and diagnostic surgery procedures, further training of primary health care doctors. Implementation of proposed activities will significantly (by 3-5 times) reduce the time for diagnostics of respiratory system disease.

[Pathomorphological changes in the lung in tuberculosis patients died from HIV infection at the stage of AIDS].

The authors revealed the typical morphological changes of lung tuberculous lesion in HIV infection at the stage of AIDS: these included alterative changes without typical tuberculosis granulomas; a well-defined exsudative inflammatory component with a predominance of leukocytic infiltration and a drastically decrease of and, occasionally, a complete disappearance of macrophages and lymphocytes; formation of pyonecrotic foci; the focal monomorphic pattern illustrating the loss of the signs of process indulation. These signs suggest the specific features of immunity and the course of specific inflammation as immediate hypersensitivity with the acutest progression of tuberculosis.

[Morphological signs of acute lung lesion in patients with caseous pneumonia].

The authors conducted light optical and electron microscopic studies of caseum-free resected lung parenchymal portions from 11 patients with caseous pneumonia. All cases were found to have severe vascular bed permeability impairments, developed extensive intraalveolar edema, destruction of both type 1 respiratory alveolocytes and surfactant-producing type 2 alveolocytes. Release of plasma proteins into the intraalveolar space and their interaction with extracellular phospholipoproteins gave rise to hyaline masses.

[On the morphological diagnosis of drug-resistant pulmonary tuberculosis].

The intraoperative samples taken from 15 patients with acutely progressive drug-resistant fibrocavernous pulmonary tuberculosis were studied. There were typical signs of granulomatosis inflammation, a predominance of an exudative tissue reaction, and an extensive vascular bed lesion. Two types of perifocal cellular infiltrates were identified. Mononuclear infiltrates with epithelioid cellular transformation along the periphery were defined as specified. Nonspecific infiltrates were composed of foam macrophages-lipophages and they reflected lipid metabolic disturbances. In addition, the severity of the process was determined by an extensive specific bronchial lesion of all generations. A morphological study of the samples could reveal the tissue and cellular features of respiratory organs in drug-resistant tuberculosis and identify the diagnostically significant signs of specific and nonspecific inflammation.

[Impact of phthisiosurgery on the development of morphological studies of the lung].

The paper describes the most important developmental stages of phthisiomorphology in chronological order, by using as an example the work of the Pathomorphology Laboratory, Central Tuberculosis Research Institute, since its organization. It also shows the stages of phthisiosurgery with the inestimable scientific and practical contribution of the works by L. K. Bogush and his followers from the formation of lung surgery to today's achievements. The authors give examples of the long-term working partnership of surgeons and morphologists in the development of these two disciplines, which was fruitful in deciding many issues of phthisiology.

[Leukinferon in combined therapy for acute pulmonary tuberculosis]. / Leikinferon v kompleksnoi terapii ostroprogressiruiushchego tuberkuleza legkikh.

Experiments on 140 CBA and C57BL/6 mice and studies of 163 patients with acute pulmonary tuberculosis have indicated that leukinferon has a immunomodulating effect on morphological reactions in the lung and on the clinical course of the disease. They have shown that leukinferon plays an important role in the activation of exudate macrophages and in the acceleration of their differentiation in experimental tuberculosis and that there is a rapid elimination of Mycobacterium tuberculosis from the involved organs without production of the L-forms of the causative agent when immunomodulation is used. At months 2-3, the patients with acute pulmonary tuberculosis showed the accelerated processes of detoxification, abacillation, infiltrate resolution, and decay cavity closure during hemo- and immunomodulation with the normalized production of cytokines (gamma-interferon and tumor necrosis factor-alpha). During 6-month therapy, a severe pulmonary process was arrested in 84% of cases and some patients were operated on (76% in the comparison group). The morphological effect of leukinferon was to increase mononuclear infiltration and to normalize a lung connective tissue response, by further decreasing the rate of inflammation.

[Specific features of the macrophage formula of bronchoalveolar lavage in patients with destructive pulmonary tuberculosis]. / Osobennosti makrofagal'noi formuly bronkhoal'veoliarnogo smyva u bol'nykh destruktivnym tuberkulezom legkikh.

The macrophageal elements (ME) of bronchoalveolar lavage were cytologically and electron microscopically studied in 11 patients with active pulmonary tuberculosis who took antituberculous drugs during 3-6 months, which did not yield a significant clinical effect (Group 1) and in 24 patients with the disease who received inhaled C-BL during chemotherapy (Group 2). The drug was administered in a dose of 20 mg by a nebulizer every second day during 4-9 weeks. In Group 1, the high levels of young biosynthesizing (32.08 +/- 0.10) and mature secreting (11.50 +/- 0.70) ME were combined with the lower counts of phagocytizing macrophages (11.50 +/- 0.90). In Group 2, the specific features depended on the duration of C-BL use and after 20-28 inhalations their composition tended to normalize: biosynthesizing (18.30 +/- 1.05), secreting (5.80 +/- 0.95), and phagocytizing (47.20 +/- 1.05). In 19 patients from Group 2, the therapeutic effect was clinically regarded as positive.

[Morphological diagnosis of tuberculosis and some disseminated diseases of the lungs]. / Morfologicheskaia diagnostika tuberkuleza i nekotorykh disseminirovannykh zabolevanii legkikh.

Based on the results of light optic and electron microscopic studies of lung tissue biopsy specimens from patients with disseminated tuberculosis (n = 31), sarcoidosis (n = 46), exogenous allergic alveolitis (n = 22), the authors present a set of various morphological signs of specific inflammation, which are detectable both in the area of a focus and in its adjacent sites. The set allows the diagnosis of the most common granulomatoses of the lung to be verified.

[Features of morphological reactions in caseous pneumonia]. / Osobennosti morfologicheskikh reaktsiipri kazeoznoi pnevmonii.

The morphological features of caseous pneumonia (CP) were studied in 90 patients aged 20-54 years by using specimens obtained at autopsy and surgery at the Central Research Institute of Therapy, Russian Academy of Medical Sciences and Moscow Clinical Tuberculosis Hospital No. 7. Thirty patients died from CP, 30 were operated on for CP. A matched group of 30 patients was operated on for fibrocavernous pulmonary tuberculosis (FCPT). Of the 30 patients operated on for CP, the process was classified as an individual nosological entity in 19 patients and as a complication due to FCPT in 11 patients. Out of the 30 deceased, CP was as an individual nosological entity in 17 patients and it complicated acute FCPT in 13 patients. Morphological (light and electron microscopy) and immunomorphological studies revealed the specific features of CP, which distinguished it from other forms of pulmonary tuberculosis. These included: the fulminant course and dissemination of lung tissue lesion, which is association with the appearance of intravascular blood coagulation and lung infarction; 2) development of immunodeficiency in the presence of autoallergy to the basilar membrane of lung vessels, macrophageal and lymphocytic dysfunctions; 3) extensive cell dystrophy of the air-blood barrier even in the intact portions of the lung; 4) hepatic dysfunction due to extensive dystrophy to the extent of hepatocytic micronecroses and dyscirculatory disorders.

[Morphological characteristics of reparative process in tuberculous inflammation]. / Morfologicheskaia kharakteristika reparativnogo protsessa pri tuberkuleznom vospalenii.

The morphological analysis of the reparative process in the involvement foci and adjacent pulmonary tissue in patients with pulmonary tuberculosis and experimental animals during intensive focal resolution has revealed a change in the cellular composition: epithelioid cells are replaced by macrophages, T-lymphocytes SD8 (suppressors) by those CD4 (helpers); actively synthesizing fibroblasts and vascular endothelium appear in the area of specific inflammation instead of the cells that have a decreased collagen-forming function. The employment of various methods for stimulation of cellular reactions (lasers, electromagnetic irradiation of the mm range - MM waves, the complex of cytokines) leukinferon enables one to alter the qualitative and quantitative cellular composition of granulomas, the rate of metabolic processes and the differentiation of cells, as well as to examine the regularities of reparative reactions more effectively and more purposefully. The perfocally adjacent pulmonary tissue wherein the diseased parenchyma and stroma recover has been ascertained to be also involved into the reparative process.