Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype

Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known. Methodology/Principal Findings: Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications. Conclusions/Significance: The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.Original Publication:Charlotte Gustafsson (Lidström), Jenny Mjösberg, Andreas Matussek, Robert Geffers, Leif Matthiesen, Göran Berg, Surendra Sharma, Jan Buer and Jan Ernerudh, Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype, 2008, PLoS ONE, (3), 4, e2078.http://dx.doi.org/10.1371/journal.pone.0002078Copyright: Public Library of Science (PLoS)http://www.plos.org

Hypogonadism in chronic obstructive pulmonary disease (COPD) - risk factors

© 2019 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Bacground/Aim. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality in pulmonary pathology. However, apart from its own pulmonary manifestations, this disease is also characterized by systemic effects, including hypogonadism which is described especially in the group of men with COPD. The aim of this study was to evaluate risk factors for hypogonadism in men with COPD. Methods. The study included 96 male patients with COPD in stable phase of the disease. All patients were checked for concentration of free testosterone in serum, markers of systemic inflammation, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and C reactive protein (CRP), pulmonary function test, gas exchange parameters, a 6-minute walk test (6MWT), nutritional status and condition of skeletal muscle (midthigh muscle cross-sectional area - MTCSA using computed tomography). Results. Decreased value of free testosterone was found in 37.5% of the patients. In the group with hypogonadism (free testosterone < 4.5 pg/mL), we found significantly increased serum concentration of TNF-α (5.88 ± 3.21 vs. 3.16 ± 2.53 pg/mL; p < 0.05), significantly lower MTSCA (68.2 ± 18.72 vs. 91.1 ± 21.4 cm2; p < 0.05) and the 6MWT (268.33 ± 32.35 vs. 334.25 ± 43.25 m; p < 0.05). Lung function, gas exchange markers and body mass index (BMI) were similar in both groups. The multivariate regression analysis singled out serum value of TNF-α as an independent predictor of serum concentrations of free testosterone (B = -0.157; 95% confidence interval: -0.262-0.053). Conclusion. In our analysis we found that TNF-α as a marker of systemic inflammation is an independent predictor of the presence of hypogonadism in the patients with COPD. Our results indicate that hypogonadism predisposes to skeletal muscle wasting and exercise intolerance in male COPD patients

Does the severity of obstructive sleep apnea have an independent impact on systemic inflammation?

Background and Objectives: This paper aims to show whether obstructive sleep apnea (OSA) severity increases the level of systemic inflammation markers regardless of body mass index (BMI) and body composition. Materials and Methods: In total, 128 patients with OSA were included in the study. Examinees were divided into two groups: one with mild OSA (apnea–hypopnea index (AHI) < 15) and one with moderate and severe OSA (AHI ≥ 15). Nutritional status was assessed using body mass index, body composition by dual X-ray absorptiometry. Systemic inflammation was assessed on the basis of plasma concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and serum level of C-reactive protein (CRP). Results: We found elevated mean values of the evaluated systemic inflammation markers (CRP, TNF-α, IL-6) in a group with AHI ≥ 15, although there was no statistical significance. Our research found a significant positive correlation with BMI (r = 0.633, p < 0.001), as well as with body fat percentage (r = 0.450, p = 0.024) and serum CRP values. Significant correlation was found between the plasma IL-6 concentration and body fat percentage (FM%) (r = 0.579, p = 0.003) and lean body mass (r = −0.501, p = 0.013). Multivariate regression analysis did not show any independent predictor (parameters of OSA, nutritional status, body composition) of the systemic inflammation markers. Conclusions: Neither one tested parameter (nutritional status and body composition) of the severity of OSA was identified as an independent prognostic factor for the severity of systemic inflammation in patients with OSA

The presence of functional mannose receptor on macrophages at the maternal–fetal interface

BACKGROUND: The mannose receptor (MR) is involved in the initiation of the immune response and regulation of homeostasis during inflammation and tissue remodeling. METHODS: Distribution, endocytosis and possible natural ligand tumor associated glycoprotein-72 (TAG-72) for the MR have been examined by immunohistology, immunocytochemistry and flow cytometry at the maternal–fetal interface, characterized by extensive tissue remodeling. RESULTS: Contrary to disseminated distribution of the MR positive (MR+) cells in term placenta, the MR+ cells of early pregnancy decidua intimately surrounded glands and followed tissue distribution of CD14 positive cells. The mannose receptor was present on freshly isolated first trimester decidual mononuclear cells and distributed mostly on macrophages (77.08 ± 10.55%, mean ± SD). The expression of the MR on CD14 positive cells decreased following 18 h culture (P<0.01) and was accompanied by the reduction of fluorescein isothiocyanate (FITC)–dextran uptake. PAM-1 anti-MR antibody, mannan and TAG-72 reduced FITC–dextran uptake by decidual macrophages. CONCLUSIONS: These data indicate that the MR+ macrophages, surrounding early decidual glands, are able to internalize ligands for carbohydrate recognition domain of the receptor, including decidual secretory phase mucin TAG-72