Presence Of Foamy Macrophages Research Articles

Mycobacterium tuberculosis response to cholesterol is integrated with environmental pH and potassium levels via a lipid metabolism regulator.

Successful colonization of the host requires Mycobacterium tuberculosis (Mtb) to sense and respond coordinately to disparate environmental cues during infection and adapt its physiology. However, how Mtb response to environmental cues and the availability of key carbon sources may be integrated is poorly understood. Here, by exploiting a reporter-based genetic screen, we have unexpectedly found that overexpression of transcription factors involved in Mtb lipid metabolism altered the dampening effect of low environmental potassium concentrations ([K+]) on the pH response of Mtb. Cholesterol is a major carbon source for Mtb during infection, and transcriptional analyses revealed that Mtb response to acidic pH was augmented in the presence of cholesterol and vice versa. Strikingly, deletion of the putative lipid regulator mce3R had little effect on Mtb transcriptional response to acidic pH or cholesterol individually, but resulted specifically in loss of cholesterol response augmentation in the simultaneous presence of acidic pH. Similarly, while mce3R deletion had little effect on Mtb response to low environmental [K+] alone, augmentation of the low [K+] response by the simultaneous presence of cholesterol was lost in the mutant. Finally, a mce3R deletion mutant was attenuated for growth in foamy macrophages and for colonization in a murine infection model that recapitulates caseous necrotic lesions and the presence of foamy macrophages. These findings reveal the critical coordination between Mtb response to environmental cues and cholesterol, a vital carbon source, and establishes Mce3R as a transcription factor that crucially serves to integrate these signals.

Rare case of microglandular-like adenocarcinoma of endometrium

This paper focuses on the microglandular-like pattern, a rare pattern of endometrial carcinoma whose appearance resembles microglandular hyperplasia of the endocervix. Its similarity with benign lesions makes diagnosis of this pattern of carcinoma difficult, particularly in minute specimens. Moreover, it raises a question of whether the tumor originates from the uterine corpus or the cervix. Microglandular-like adenocarcinoma of the endometrium may be an individual type of carcinoma or combined with endometrioid or mucinous carcinoma. The immunohistochemical evaluation is recommended for precise diagnosis: microglandular-like adenocarcinoma expresses markers typical for cervical carcinomas (p16, СК17, and carcinoembryonic antigen) and endometrial carcinomas (estrogen, vimentin, and CD10). The presence of foamy macrophages in the stroma of the tumor and intraglandular foci of squamous differentiation help in the differential diagnosis of microglandular hyperplasia of the endocervix. Immunohistochemical evaluation also facilitates differential diagnosis: a negative PAX2 expression and a high mitotic index (Ki-67 10%) indicate a microglandular-like adenocarcinoma.

Adult-Onset Asthma With Periocular Xanthogranuloma: Clinical-Histological Correlation.

A 48-year-old male presented with 10 years of gradually enlarging yellow eyelid lesions. Past medical history was notable for adult-onset asthma diagnosed 5 years ago. He denied pain, diplopia, bone/joint pain, or systemic findings such as weight loss or fatigue. His father had similar eyelid lesions. Preoperative photograph demonstrated bilateral upper eyelid yellowish lesions with prominent edema and tissue expansion inducing bilateral ptosis (Fig. 1A). MRI demonstrated eyelid inflammation, enlargement of the extraocular muscles, especially the right lateral rectus (Fig. 1B, white arrow), and enlargement and enhancement of lacrimal gland (Fig. 1C, black arrow). He desired debulking excisional biopsies with bilateral blepharoplasty. Intraoperative photos show significant soft tissue inflammatory infiltration, particularly the lacrimal gland (Fig. 1D, red arrows).FIG. 1.Histopathologically, xanthogranulomatous inflammation is characterized by diffuse inflammatory infiltrate composed of histiocytes and lymphocytes (Fig. 2A, H&E, 100×). Specifically, the presence of foamy macrophages (Fig. 2B, H&E, 400×, red arrows) and Touton Giant cells (Fig. 2C, H&E, 400×, black arrow) are the histological hallmarks of the disease. The differential diagnosis of xanthogranulomatous inflammation includes adult-onset xanthogranuloma, adult-onset asthma with periocular xanthogranuloma (AAPOX), Erdheim-Chester disease (ECD), necrobiotic xanthogranuloma (NBX), and juvenile xanthogranuloma.FIG. 2.The patient was diagnosed with AAPOX given the association with adult-onset asthma. While the vast majority of yellow eyelid lesions are clinically benign, ECD and NBX are must-not-miss diagnoses, given their potential life-threatening systemic manifestations. These include vital organ (heart/kidney/lung) involvement in ECD, and association with serum protein abnormalities and hematological malignancies in NBX.

Solitary nodule on the forearm

Herein, we report the case of a 58-year-old male who presented himself with a single, slowly progressive, asymptomatic lesion on the right forearm persistent for the last three years. Clinical evaluation revealed a single firm reddish nodule. Histopathological findings from a complete excision revealed a lipidized dermatofibroma, which was characterized by the accumulation of numerous foamy cells dissected by distinctive hyalinized wiry collagen fibers and the presence of foamy macrophages. Lipidized dermatofibroma—a rare variant of dermatofibroma—must be considered in the differential diagnosis of fibrohistiocytic lesions.

Efficacy of Vitex agnus in lowering prolactin level in mammary tumor induced SD rats

Introduction and Aim: Breast cancer accounts for about 30% of all cancers in women. The present study aims to see the role of prolactin and Vitex agnus fruit extract in breast cancer progression in mammary tumor induced Sprague Dawley (SD) rats.
 Materials and Methods: Thirty-day old inbred SD female rats of body weight 70-80 grams were taken for this study. The rats were induced with N- Methyl-Nitroso-Urea for mammary tumor development. After the development of palpable and visible tumor the rats were treated with anti-prolactin drug (Cabergoline) and a prolactin lowering herb Vitex agnus Castus (VAC) for two months. After the treatment the rats were sacrificed for antioxidants estimation and histopathological section examination.
 Results: The rats treated with anti-prolactin drug showed benign tumors with hyperplasia and lactational change proving the presence of prolactin in the tumor tissue, whereas the plant extract showed mammary tumor regression by the presence of foamy macrophages in the histopathological sections. Results also showed treatment with cabergoline increased the GSH level and decreased the MDA level compared to tumor induced group.
 Conclusion: Prolactin may have a potential role in progression of breast cancer and Vitex agnus extract showed a prolactin lowering effect and facilitated in regression of the tumor.

Malacoplakia of the skin: overview of a rare clinical entity

Malacoplakia is a rare acquired, infection-related granulomatous disorder, that may affect many systems, but typically occurs in the urinary tract. Cutaneous involvement is less prevalent, and most commonly presents with a perianal or genital region localization. Cutaneous malacoplakia is believed to be caused by an acquired bactericidal defect of macrophages in the setting of chronic infections and immunocompromised states. A diagnosis of cutaneous malacoplakia should be considered when encountering non-specific granulomatous lesions that are refractory to treatment. Histologic findings are marked by the presence of foamy macrophages containing the pathognomonic Michaelis-Gutman bodies. The aim of this review is to discuss the current perspectives on the pathophysiology, clinical features, diagnosis, and treatment of this disease. We would also like to emphasize that the integration of clinical information, microscopic findings, and exclusion of other cutaneous granulomatous processes is necessary to accurately diagnose this exceedingly rare disease and provide opportunity for therapeutic intervention. Data for this work were collected from the published literature and textbooks. Combined surgical excision and protracted antibiotic courses appear to have the highest success rate. Antibiotics should be culture specific, but drugs that easily permeate the macrophages appear to be the best choice.

Characterization and Frequency of Histological Changes in Bovine Livers from Slaughterhouses in Brazil kept on Brachiaria spp.

Background: Brachiaria spp. is the main pasture for ruminant productions in Brazil, but the limiting factor for its use is the toxicity due to the presence of steroidal saponins. Chronic ingestion of Brachiaria spp. by cattle may cause liver changes such as fibrosis, bile duct proliferation and clusters of foamy macrophages in the hepatic parenchyma. The main objective of the present study was to evaluate the most frequent histological changes and their frequencies in livers collected in abattoirs in Brazil from beef cattle raised exclusively on Brachiaria spp. and compare them with those observed in animals kept in Andropogon spp. grass and native pastures in Rio Grande do Sul.Materials, Methods & Results: Liver samples without macroscopic changes were collected in abattoirs from 561 healthy Nelore and Nelore crossbred cattle raised in Brachiaria spp. pastures from Mato Grosso (MT), Mato Grosso do Sul (MS), Minas Gerais (MG) and Pará (PA) States. Liver samples from 84 Angus cattle (Bos taurus) kept on native pastures in Rio Grande do Sul (RS) and from 60 Nelore and Nelore crossbreed cattle raised in Andropogon spp. pastures in Tocantins State (TO) were collected as control. Semi-quantitative analysis of the histopathological changes were proceeded: (-) = no change; (+) = slight or discreet change; (++) = moderate change and (+++) = marked change. The main histopathological changes evaluted in the liver samples were the presence of foamy macrophages and its location, parenchymal fibrosis and its location, proliferation of bile ducts, periportal mononuclear infiltrate, presence of crystals in macrophages and within the bile ducts. Foamy macrophages clusters in the liver parenchyma were the most frequent histological changes exclusively observed in samples of animals kept in Brachiaria spp. and it was more frequent in cattle from MS State (P < 0.0001). The periportal hepatic fibrosis was another relevant finding in cattle kept in Brachiaria spp. and was also more frequent in MS animals (P ≤ 0.0001), and was not present in control groups. Proliferation of the bile ducts rate was similar between animals raised in Brachiaria spp. (P > 0.05), though it was higher in cattle kept on native pasture in RS (P < 0.0001). The mononuclear periportal inflammatory infiltrate was more frequent in MS and MG samples than in MT and PA (P < 0.0002).Discussion: The most significant histopathological changes observed in liver samples of cattle from the states of MT, MS, PA and MG kept in Brachiaria spp. pastures from the birth to slaughter, was the presence of foamy macrophages in quantities and variables distribution showing the strengthen association between clusters of foamy macrophages in the liver parenchyma and grazing on this grass. These macrophages could be found in healthy animals kept in Brachiaria spp. pastures and in intoxicated animals. This change was considered frequent and characteristic in animals kept in pastures containing steroidal lithogenic saponins in its composition, and it was frequently observed in ruminants that growed in Brachiaria spp. pastures. Beef cattle kept in Andropogon spp. grass pastures in the state of Tocantins and native pastures in Rio Grande do Sul did not showed foamy macrophages in liver samples. On the other hand, in susceptible sheep kept in Andropogon spp. grass pastures that contains low amount of lithogenic steroidal saponins, are insufficient to induce toxicity and morphological changes in the liver, including aggregates of foamy macrophages.

Papillary renal cell carcinoma-derived chemerin, IL-8, and CXCL16 promote monocyte recruitment and differentiation into foam-cell macrophages

Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma. The only curative treatment available for pRCC is radical surgery. If the disease becomes widespread, neither chemo- nor radiotherapy will have therapeutic effect, hence further research on pRCC is of utmost importance. Histologically, pRCC is characterized by a papillary growth pattern with focal aggregation of macrophages of the foam cell phenotype. In other forms of cancer, a clear role for tumor-associated macrophages during cancer growth and progression has been shown. Although the presence of foamy macrophages is a histological hallmark of pRCC tumors, little is known regarding their role in pRCC biology. In order to study the interaction between pRCC tumor and myeloid cells, we established primary cultures from pRCC tissue. We show that human pRCC cells secrete the chemokines IL-8, CXCL16, and chemerin, and that these factors attract primary human monocytes in vitro. RNAseq data from The Cancer Genome Atlas confirmed a high expression of these factors in pRCC tissue. Conditioned medium from pRCC cultures induced a shift in human monocytes toward the M2 macrophage phenotype. In extended cultures, these macrophages became enlarged and loaded with lipids, adopting the foam cell morphology found in pRCC tissue. These results show for the first time that pRCC primary tumor cells secrete factors that attract and differentiate monocytes into anti-inflammatory tumor-associated macrophages with foam cell histology.

Encephalic xanthomas in a large malayan chevrotain ( Tragulus napu )

An adult water chevrotain was euthanized due to severe non-responsive pododermatitis. Incidentally, multiple to coalescing cholesterol granulomas were identified within the right diencephalon, characterized by the presence of foamy macrophages and cholesterol clefts consistent with encephalic xanthomas. No clinical signs or predisposing conditions associated with this finding were identified. This is the first known report of encephalic xanthomas in this species.

Whipple's in the valleys: a case of Whipple's with thrombocytopenia and endocarditis

IntroductionThis case report details the second described case of Whipple's disease-related thrombocytopenia in the medical literature. Whipple's disease is a rare multisystem infection caused by the actinomycete Tropheryma whipplei, first...

S22 Analysis of the lung microbiome in human asthma using whole genome shot-gun metagenomics

Introduction and ObjectivesEvidence is accumulating for the presence of bacteria in the airways and the existence of a commensal airway microbiome. Molecular techniques reveal complex microbial assemblages in bronchiectasis and...

Alveolar Foamy Macrophages and Mast Cells in Bronchoalveolar Lavage of Methotrexate-induced Pneumonitis

Methotrexate-induced pneumonitis (MTX-P) is an unusual adverse drug reaction that typically manifests as an interstitial lung disease (ILD). Early diagnosis of this complication is desirable because discontinuation of MTX with or without steroid administration often results in a fast recovery. Conversely, a delay or a misdiagnosis may lead to death. Diagnostic workup is often problematic because underlying diseases leading to methotrexate administration, notably rheumatoid arthritis (RA), and opportunistic infections because of drug-induced immune impairment can also produce an ILD. In this clinical setting, bronchoalveolar lavage (BAL) plays a key role either in excluding infectious agents, especially in febrile presentations, or in looking for malignant cells. Unfortunately, BAL does not have specific features to allow clinicians to differentiate MTX-P from RA-associated ILD. Here, we present 2 definite cases of MTX-P in RA patients. BAL differential cell counts and alveolar CD4/CD8 values were found to be in agreement with those reported in the literature, but an increase in mast cells and the presence of foamy macrophages have never been reported among previously published cases. The presence of both mast cells and foamy macrophages could be helpful in differentiating MTX-P from many drug-unrelated ILDs, but does not assist in distinguishing MTX-P from Pneumocystis jiroveci pneumonia and RA-associated bronchiolitis obliterans organizing pneumonia.

Avaliação da exposição solar na intoxicação experimental por Brachiaria decumbens em ovinos

Foram utilizados 26 ovinos, entre 3 e 4 meses de idade, divididos em 3 grupos, provenientes de rebanhos que nunca tiveram contato com pastos de Brachiaria spp.. Dois grupos receberam Brachiaria decumbens no cocho diariamente ad libitum, sendo que um deles permaneceu em área com exposição solar (GS) e o outro foi mantido em baias cobertas protegidos do sol (GSB). O grupo controle (GC) foi também mantido em local com exposição solar e alimentado com feno de Cynodon dactylon e capim Pennisetum purpureum triturado. Todos os grupos receberam alimentação em cochos e foram suplementados com 200g/dia/animal de ração comercial para ovinos. Foi realizada a avaliação clínica diária dos ovinos e colhidas amostras duas vezes por semana para dosagem sérica de AST e GGT. Os animais que morreram foram submetidos a necropsia e em todos os ovinos sobreviventes foi realizada biópsia hepática no final do experimento. Três animais do grupo GS adoeceram e dois morreram. Um ovino do grupo GSB adoeceu e morreu. Não houve alterações clínicas nos ovinos controles. Os principais sinais clínicos observados nos animais que adoeceram foram apatia, emagrecimento, fotofobia, hiperemia e secreção ocular e icterícia. Nenhum animal apresentou lesões cutâneas de fotossensibilização. O grupo que permaneceu no sol apresentou atividades séricas médias de AST e GGT significativamente maiores que a dos demais grupos (p<0,05) e os animais que permaneceram na sombra apresentaram níveis maiores de GGT (p<0,05) em comparação ao grupo controle. A histopatologia das amostras de fígados dos ovinos com sinais clínicos demonstrou tumefação e vacuolização de hepatócitos, necrose individual de hepatócitos, macrófagos espumosos com cristais birrefringentes intracitoplasmáticos e dentro de ductos biliares e infiltrado mononuclear periportal. Amostras do capim fornecidas aos cordeiros evidenciaram níveis médios de 0,94±0,80% da saponina protodioscina. As observações do presente experimento sugerem que a não exposição ao sol não evita a presença de sinais clínicos da intoxicação, mas que a exposição solar exacerba os sinais clínicos.

Targeted Deletion of Jun/AP-1 in Alveolar Epithelial Cells Causes Progressive Emphysema and Worsens Cigarette Smoke–Induced Lung Inflammation

Chronic obstructive pulmonary disease appears to occur slowly and progressively over many years, with both genetic factors and environmental modifiers contributing to its pathogenesis. Although the c-Jun/activator protein 1 transcriptional factor regulates cell proliferation, apoptosis, and inflammatory responses, its role in lung pathogenesis is largely unknown. In this study, we report decreased expression levels of c-Jun mRNA and protein in the lung tissues of patients with advanced chronic obstructive pulmonary disease, and the genetic deletion of c-Jun specifically in alveolar epithelial cells causes progressive emphysema with lung inflammation and alveolar air space enlargement, which are cardinal features of emphysema. Although mice lacking c-Jun specifically in lung alveolar epithelial cells appear normal at the age of 6 weeks, when exposed to long-term cigarette smoke, c-Jun-mutant mice display more lung inflammation with perivascular and peribronchiolar infiltrates compared with controls. These results demonstrate that the c-Jun/activator protein 1 pathway is critical for maintaining lung alveolar cell homeostasis and that loss of its expression can contribute to lung inflammation and progressive emphysema.

Lipid Droplets andMycobacterium lepraeInfection

Leprosy is a chronic infectious disease and is a major source of morbidity in developing countries. Leprosy is caused by the obligate intracellular bacterium Mycobacterium leprae, which infects as primary target Schwann cells. Lepromatous leprosy exhibits multiple lesions of the skin, eyes, nerves, and lymph nodes. The sites of infection are characterized by the presence of foamy macrophages, fully packed with lipid droplets (LDs), which are induced by M. leprae. In the last years, it has become evident that M. tuberculosis imports lipids from foamy macrophages and is dependent on fatty acids for growth in infected macrophages. M. leprae seems to have similar mechanisms for scavenging lipids from the host. But due to the inability to culture M. leprae on laboratory media, research progresses only slowly. However, in the last years, substantial progress has been made in the field of lipid metabolism in M. leprae. Herein, we will present and summarize the lipid droplets formation and the metabolism of lipids during M. leprae infection.

Rozpoznawanie i leczenie mikroskopowego zapalenia jelita grubego z obecnością makrofagów piankowatych u dzieci

The aimDiagnosis and efficacy of 5-amino-2-hydroxybenzoic acid (5-ASA) or Saccharomyces boulardii or magnesium in therapy of microscopic colitis with presence of foamy macrophages in children Material and methodsThe basis for diagnosis and inclusion to the analysed group was presence of characteristic foamy macrophages in histological examination of hematoxylin end eosin-stained specimens collected from the large intestine, reviewed in microscope under x 200 or x 320 magnification. 144 children were included to the analysis. For 12 months 38 children were treated with mesalasine (5-amino-2-hydroxybenzoic acid), 35 children received Saccharomyces boulardii and 35 children were treated with magnesium aspartate. The control group consisted of 36 children who received no therapy. ResultsNo statistically significant improvement was found following the use of 5-amino-2-hydroxybenzoic acid in therapy of the disease. The use of Saccharomyces boulardii was associated with statistically significant improvement in clinical, endoscopic and histological condition. The treatment with magnesium caused a histological, statistically significant improvement, but failed to have any effect on the clinical and endoscopic presentation. In the group of children in whom none therapeutic intervention was provided, a statistically significant spontaneous clinical improvement was observed, but no statistically significant changes in endoscopic and microscopic condition were found. ConclusionsEfficacy of the therapy with probiotic Saccharomyces boulardii was confirmed in patients with microscopic colitis with presence of foamy macrophages. No fitness of 5-amino-2-hydroxybenzoic acid for therapy of the disease was demonstrated. Untreated children present a tendency for spontaneous clinical remission. A 12-month follow-up in that group showed no progression of endoscopic and microscopic lesions.

Diagnosis and therapy of microscopic colitis with presence of foamy macrophages in children.

We discuss the diagnosis of and efficacy 5-amino-2-hydroxybenzoic acid (5-ASA), Saccharomyces boulardii, or magnesium in therapy of microscopic colitis with presence of foamy macrophages. A basis for diagnosis and inclusion to the analysed group was presence of characteristic foamy macrophages in histopathological examination of hematoxylin and eosin-stained specimens collected from the large intestine, reviewed under ×200 or ×320 magnification. No statistically significant improvement was found following the use of 5-amino-2-dihydroxybenzoic acid in therapy of the disease. The use of Saccharomyces boulardii was associated with statistically significant improvement in clinical, endoscopic, and histopathological condition. Use of magnesium caused a histological, statistically significant improvement but failed to have any effect on the clinical and endoscopic presentation. In the group of children in whom no therapeutic intervention was provided, a statistically significant spontaneous clinical improvement was observed, but no statistically significant changes in endoscopic and microscopic condition were found.

Endogenous lipid pneumonia in rats after subacute exposure to CdCl2

The objective of this report was to study lung cellular lesions in Wistar rats after subacute oral exposition to CdCl(2). The experimental groups were exposed to CdCl(2), through their drinking water in a concentration of 1 g/L, continuously for a period of 9 days. Histologically, all the exposed animals showed the incidence of interstitial pneumonia; hyperplasia of type II pneumocytes and Clara cells; the presence of foamy macrophages; and lesions linked to the existence of endogenous lipid pneumonia. Endogenous lipid pneumonia after CdCl(2) exposure has not been previously described; and in its pathogenesis, hyperplasia of type II pneumocytes and Clara cells activation could play an important role.

Relative Levels of M-CSF and GM-CSF Influence the Specific Generation of Macrophage Populations during Infection withMycobacterium tuberculosis

Members of the CSF cytokine family play important roles in macrophage recruitment and activation. However, the role of M-CSF in pulmonary infection with Mycobacterium tuberculosis is not clear. In this study, we show the lungs of mice infected with M. tuberculosis displayed a progressive decrease in M-CSF in contrast to increasing levels of GM-CSF. Restoring pulmonary M-CSF levels during infection resulted in a significant decrease in the presence of foamy macrophages and increased expression of CCR7 and MHC class II, specifically on alveolar macrophages. In response to M-CSF, alveolar macrophages also increased their T cell-stimulating capacity and expression of DEC-205. These studies show that the levels of expression of M-CSF and GM-CSF participate in the progression of macrophages into foamy cells and that these cytokines are important factors in the differentiation and regulation of expression of dendritic cell-associated markers on alveolar macrophages. In addition, these studies demonstrate that M-CSF may have a role in the adaptive immune response to infection with M. tuberculosis.

Whipple Disease: Intestinal Infiltrating Cells Exhibit a Transcriptional Pattern of M2/Alternatively Activated Macrophages

Whipple disease (WD) is a rare systemic disease caused by Tropheryma whipplei and is characterized by the presence of foamy macrophages with periodic acid-Schiff-positive inclusions in tissues such as lamina propria. For the first time, we report the gene-expression profile of macrophages in intestinal lesions from a patient with WD. Microarray and real-time polymerase chain reaction revealed that genes encoding CCL18, cathepsins, scavenger receptor, interleukin-10, and lipid metabolites were up-regulated in intestinal lesions. This transcriptional pattern corresponds to that of M2/alternatively activated macrophages. Our results suggest that the T helper 2 response in the intestinal environment may account for the pathophysiological properties of WD.