scholarly journals Adipoclast: a multinucleated fat-eating macrophage

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antoni Olona ◽  
Subhankar Mukhopadhyay ◽  
Charlotte Hateley ◽  
Fernando O. Martinez ◽  
Siamon Gordon ◽  
...  

AbstractCell membrane fusion and multinucleation in macrophages are associated with physiologic homeostasis as well as disease. Osteoclasts are multinucleated macrophages that resorb bone through increased metabolic activity resulting from cell fusion. Fusion of macrophages also generates multinucleated giant cells (MGCs) in white adipose tissue (WAT) of obese individuals. For years, our knowledge of MGCs in WAT has been limited to their description as part of crown-like structures (CLS) surrounding damaged adipocytes. However, recent evidence indicates that these cells can phagocytose oversized lipid remnants, suggesting that, as in osteoclasts, cell fusion and multinucleation are required for specialized catabolic functions. We thus reason that WAT MGCs can be viewed as functionally analogous to osteoclasts and refer to them in this article as adipoclasts. We first review current knowledge on adipoclasts and their described functions. In view of recent advances in single cell genomics, we describe WAT macrophages from a ‘fusion perspective’ and speculate on the ontogeny of adipoclasts. Specifically, we highlight the role of CD9 and TREM2, two plasma membrane markers of lipid-associated macrophages in WAT, which have been previously described as regulators of fusion and multinucleation in osteoclasts and MGCs. Finally, we consider whether strategies aiming to target WAT macrophages can be more selectively directed against adipoclasts.

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. F1-F17
Author(s):  
Rocío Martínez-Aguilar ◽  
Lucy E Kershaw ◽  
Jane J Reavey ◽  
Hilary O D Critchley ◽  
Jacqueline A Maybin

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.


1991 ◽  
Vol 261 (6) ◽  
pp. F1026-F1032 ◽  
Author(s):  
A. Vignery ◽  
M. J. Raymond ◽  
H. Y. Qian ◽  
F. Wang ◽  
S. A. Rosenzweig

The fusion of mononuclear phagocytes occurs spontaneously in vivo and leads to the differentiation of either multinucleated giant cells or osteoclasts in chronic inflammatory sites or in bone, respectively. Although osteoclasts are responsible for resorbing bone, the functional role of giant cells in chronic inflammatory reactions and tumors remains poorly understood. We recently reported that the plasma membrane of multinucleated macrophages is, like that of osteoclasts, enriched in Na-K-adenosinetriphosphatases (ATPases). We also observed that the localization of their Na-K-ATPases is restricted to the nonadherent domain of the plasma membrane of cells both in vivo and in vitro, thus imposing a functional polarity on their organization. By following this observation, we wished to investigate whether these cells also expressed, like osteoclasts, functional receptors for calcitonin (CT). To this end, alveolar macrophages were fused in vitro, and both their structural and functional association with CT was analyzed and compared with those of mononucleated peritoneal and alveolar macrophages. Evidence is presented that multinucleated alveolar macrophages express a high copy number of functional receptors for CT. Our results also indicate that alveolar macrophages, much like peritoneal, express functional receptors for calcitonin gene-related peptide. It is suggested that multinucleated rat alveolar macrophages offer a novel model system to study CT receptors and that calcitonin may control local immune reactions where giant cells differentiate.


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Elisa Lozano ◽  
Elisa Herraez ◽  
Oscar Briz ◽  
Virginia S. Robledo ◽  
Jorge Hernandez-Iglesias ◽  
...  

Changes in the uptake of many drugs by the target cells may dramatically affect the pharmacological response. Thus, downregulation ofSLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively. Moreover, the overall picture may be modified to a considerable extent by the preexistence or the appearance during the pathogenic process of genetic variants. Some rare OCT1 variants enhance transport activity, whereas other more frequent variants impair protein maturation, plasma membrane targeting or the function of this carrier, hence reducing intracellular active drug concentrations. Here, we review current knowledge of the role of OCT1 in modern liver pharmacology, which includes the use of cationic drugs to treat several diseases, some of them of great clinical relevance such as diabetes and primary liver cancer (cholangiocarcinoma and hepatocellular carcinoma). We conclude that modern pharmacology must consider the individual evaluation of OCT1 expression/function in the healthy liver and in the target tissue, particularly if this is a tumor, in order to predict the lack of response to cationic drugs and to be able to design individualized pharmacological treatments with the highest chances of success.


Author(s):  
Sônia Maria Rolim Rosa Lima

Os esteroides sexuais, em particular os estrogênios e os androgênios, representam papel fundamental, na modulação da função sexual feminina. As mulheres após a menopausa, devido ao declínio da função ovariana, são dependentes da síntese local de estrogênios nos tecidos alvo extragonadais. Mantendo-se o quadro carêncial ocorre progressivo estreitamento da vagina, e o sintoma genital mais comum é a secura por diminuição da transudação e da quantidade de muco cervical. Esses fenômenos explicam os processos encontrados no período do climatério ou qualquer período em que ocorra a carência estrogênica, característicos da falência hormonal: vaginite atrófica, leucorréia, prurido, dor e sangramento ao coito. Com relação aos androgênios, vários estudos investigaram associações entre androgênios e função sexual em mulheres. Muitos, mas não todos, identificam uma relação entre o desejo sexual e as concentrações séricas de androgênios circulantes. A variabilidade nos resultados provavelmente reflete as limitações em aferir com precisão suas baixas concentrações, o impacto potencial de outros esteroides, as diferenças no desenho do estudo, na seleção das participantes e nos parâmetros de função sexual. Neste artigo, revisamos o conhecimento atual sobre o papel dos estrogênios e androgênios e seu uso clínico em mulheres com declínio da função ovariana.Palavras chave: Hormônios sexuais, Esteroides, Androgênios, Pós-Menopausa, Disfunções sexuais fisiológicasABSTRACTSex steroids, in particular estrogens and androgens, play a fundamental role in the modulation of female sexual function. Postmenopausal women, due to the decline in ovarian function, are dependent on the local synthesis of estrogens in extragonadal target tissues. If the deficiency is maintained, progressive narrowing of the vagina occurs, and the most common genital symptom is dryness due to decreased transudation and the amount of cervical mucus. These phenomena explain the processes found during the climacteric period or any period in which estrogen deficiency occurs, which are characteristic of hormonal failure: atrophic vaginitis, leukorrhea, itching, pain and bleeding on intercourse. With regard to androgens, several studies have investigated associations between androgens and sexual function in women. Many, but not all, identify a relationship between sexual desire and serum concentrations of circulating androgens. The variability in the results probably reflects the limitations in accurately measuring the low concentrations of androgens in women, the potential impact of other steroids, the differences in the study design, in the selection of participants and in the parameters of sexual function. In this article, we review current knowledge about the role of estrogens and androgens and their clinical use in women with declining ovarian function.Keywords: Sex hormones, Steroids, Androgens, Postmenopause, Physiological sexual dysfunctions


2019 ◽  
Vol 133 (1) ◽  
pp. 23-40 ◽  
Author(s):  
Silvia Lorente-Cebrián ◽  
Pedro González-Muniesa ◽  
Fermín I. Milagro ◽  
J. Alfredo Martínez

AbstractObesity is a metabolic condition usually accompanied by insulin resistance (IR), type 2 diabetes (T2D), and dyslipidaemia, which is characterised by excessive fat accumulation and related to white adipose tissue (WAT) dysfunction. Enlargement of WAT is associated with a transcriptional alteration of coding and non-coding RNAs (ncRNAs). For many years, big efforts have focused on understanding protein-coding RNAs and their involvement in the regulation of adipocyte physiology and subsequent role in obesity. However, diverse findings have suggested that a dysfunctional adipocyte phenotype in obesity might be also dependent on specific alterations in the expression pattern of ncRNAs, such as miRNAs. The aim of this review is to update current knowledge on the physiological roles of miRNAs and other ncRNAs in adipose tissue function and their potential impact on obesity. Therefore, we examined their regulatory role on specific WAT features: adipogenesis, adipokine secretion, inflammation, glucose metabolism, lipolysis, lipogenesis, hypoxia and WAT browning. MiRNAs can be released to body fluids and can be transported (free or inside microvesicles) to other organs, where they might trigger metabolic effects in distant tissues, thus opening new possibilities to a potential use of miRNAs as biomarkers for diagnosis, prognosis, and personalisation of obesity treatment. Understanding the role of miRNAs also opens the possibility of using these molecules on individualised dietary strategies for precision weight management. MiRNAs should be envisaged as a future therapeutic approach given that miRNA levels could be modulated by synthetic molecules (f.i. miRNA mimics and inhibitors) and/or specific nutrients or bioactive compounds.


2019 ◽  
Vol 108 (1) ◽  
pp. 282-297 ◽  
Author(s):  
Ana Carolina Cestari Bighetti ◽  
Tania Mary Cestari ◽  
Paula Sanches Santos ◽  
Ricardo Vinicius Nunes Arantes ◽  
Suelen Paini ◽  
...  

2019 ◽  
Vol 71 (4) ◽  
pp. 1239-1248 ◽  
Author(s):  
Julián García Bossi ◽  
Krishna Kumar ◽  
María Laura Barberini ◽  
Gabriela Díaz Domínguez ◽  
Yossmayer Del Carmen Rondón Guerrero ◽  
...  

Abstract As sessile organisms, plants have evolved mechanisms to adapt to variable and rapidly fluctuating environmental conditions. Calcium (Ca2+) in plant cells is a versatile intracellular second messenger that is essential for stimulating short- and long-term responses to environmental stresses through changes in its concentration in the cytosol ([Ca2+]cyt). Increases in [Ca2+]cyt direct the strength and length of these stimuli. In order to terminate them, the cells must then remove the cytosolic Ca2+ against a concentration gradient, either taking it away from the cell or storing it in organelles such as the endoplasmic reticulum (ER) and/or vacuoles. Here, we review current knowledge about the biological roles of plant P-type Ca2+-ATPases as potential actors in the regulation of this cytosolic Ca2+ efflux, with a focus the IIA ER-type Ca2+-ATPases (ECAs) and the IIB autoinhibited Ca2+-ATPases (ACAs). While ECAs are analogous proteins to animal sarcoplasmic-endoplasmic reticulum Ca2+-ATPases (SERCAs), ACAs are equivalent to animal plasma membrane-type ATPases (PMCAs). We examine their expression patterns in cells exhibiting polar growth and consider their appearance during the evolution of the plant lineage. Full details of the functions and coordination of ECAs and ACAs during plant growth and development have not yet been elucidated. Our current understanding of the regulation of fluctuations in Ca2+ gradients in the cytoplasm and organelles during growth is in its infancy, but recent technological advances in Ca2+ imaging are expected to shed light on this subject.


1999 ◽  
Vol 30 (11) ◽  
pp. 1383-1388 ◽  
Author(s):  
Silloo B Kapadia ◽  
Clayton A Wiley ◽  
Virawudh Soontornniyomkij ◽  
Guoji Wang ◽  
Steven H Swerdlow

2021 ◽  
Author(s):  
liu wenzhong ◽  
Li hualan

COVID-19 is a unique disease characterized by extensive pulmonary thrombosis and infected syncytial multinucleated giant cells, relating to extensive tissue damage. The SARS-CoV-2 S protein on the membrane of infected cells can initiate receptor-dependent syncytia formation. To study the membrane fusion on S protein, we adopted structural domain search methods to analyze the structural and non-structural proteins of the SARS-COV-2 virus in this study. The results showed that the surface glycoprotein (S) had conserved domains of CaMKII: CaMKII_AD, CaATP_NAI, DUF4440, EF-hand, Protein kinase, and SnoaL-like. Comparing to SARS-COV and MERS, only the CaATP_NAI of SARS-COV-2 is in the contact position of the viral membrane and cell membrane. We believed that when the EF-hand domain (“YEQYIKWPWYIWLGF”) of S protein bound to calcium ions, S2 protein had CaMKII protein activities. After the S protein fusion peptide was inserted into the infected cell membrane and fixed the S2 protein on the cell membrane, the CaMKII_AD prompted the S2 protein to form HR1-HR2 six-helix bundles. The HR1-HR2 hexamer had three CaATP_NAI domains (“APAICHDGKAHFPRE”) near the viral membrane (contact position), the CaATPase activated by magnesium ions, and released energy through ATP phosphorylation. The CaATPase drove the HR1-HR2 hexamer fold irreversibly toward the viral membrane. Then the CaATP_NAI and CaMKII_AD domains extended to the outside and combined the viral membrane and the cell membrane so that the contact position formed a thin barrel structure. The hydrated calcium ions are gathered in the barrel structure to create a calcium bridge. The release action of water in contact position caused the instability of the double membrane, triggering lipid mixing and fusion of the membrane. CaATPases disassembled the barrel structure, and HR1-HR2 hexamer is fell into the cytoplasm. The viral membrane fused with the cell membrane on a large scale. The cytoplasmic contents of the virus mixed with the cell. The S protein of the infected cell may bind to the ACE2 receptor of another cell (or also an infected cell) and then achieved membrane fusion through a similar principle, forming cell syncytia, includes syncytial multinucleated giant cells. The membrane fusion could disrupt the calcium homeostasis in human body, and increased the risk of coagulation and vascular calcification.


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