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Results and Problems in Cell Differentiation

Yianzhu Liu, Jacek Z Kubiak, Xian C Li, Rafik M Ghobrial, Malgorzata Kloc
RhoA is a small GTPase that, via its downstream effectors, regulates a variety of cell functions such as cytokinesis, cell migration, vesicular trafficking, and phagocytosis. As such the RhoA pathway is also pivotal for proper functioning of immune cells including macrophages. By controlling actin cytoskeleton organization, RhoA pathway modulates macrophage's polarity and basic functions: phagocytosis, migration, and extracellular matrix degradation. Numerous studies indicate that macrophages are very important effectors contributing to acute and chronic rejection of transplanted organs...
2017: Results and Problems in Cell Differentiation
Girish J Kotwal, Sufan Chien
Chronic wounds pose considerable public health challenges and burden. Wound healing is known to require the participation of macrophages, but mechanisms remain unclear. The M1 phenotype macrophages have a known scavenger function, but they also play multiple roles in tissue repair and regeneration when they transition to an M2 phenotype. Macrophage precursors (mononuclear cells/monocytes) follow the influx of PMN neutrophils into a wound during the natural wound-healing process, to become the major cells in the wound...
2017: Results and Problems in Cell Differentiation
Jamie E Rayahin, Richard A Gemeinhart
Macrophages are the initial biologic responders to biomaterials. These highly plastic immune sentinels control and modulate responses to materials, foreign or natural. The responses may vary from immune stimulatory to immune suppressive. Several parameters have been identified that influence macrophage response to biomaterials, specifically size, geometry, surface topography, hydrophobicity, surface chemistry, material mechanics, and protein adsorption. In this review, the influence of these parameters is supported with examples of both synthetic and naturally derived materials and illustrates that a combination of these parameters ultimately influences macrophage responses to the biomaterial...
2017: Results and Problems in Cell Differentiation
Kylie B R Belchamber, Louise E Donnelly
In the healthy lung, macrophages maintain homeostasis by clearing inhaled particles, bacteria, and removing apoptotic cells from the local pulmonary environment. However, in respiratory diseases including chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis, macrophages appear to be dysfunctional and may contribute to disease pathogenesis. In COPD, phagocytosis of bacterial species and apoptotic cells by both alveolar macrophages and monocyte-derived macrophages is significantly reduced, leading to colonization of the lung with pathogenic bacteria...
2017: Results and Problems in Cell Differentiation
Yuri V Bobryshev, Nikita G Nikiforov, Natalia V Elizova, Alexander N Orekhov
Atherosclerosis can be regarded as chronic inflammatory disease driven by lipid accumulation in the arterial wall. Macrophages play a key role in the development of local inflammatory response and atherosclerotic lesion growth. Atherosclerotic plaque is a complex microenvironment, in which different subsets of macrophages coexist executing distinct, although in some cases overlapping functions. According to the classical simplified nomenclature, lesion macrophages can belong to pro-inflammatory or anti-inflammatory or alternatively activated types...
2017: Results and Problems in Cell Differentiation
Lewis Gaffney, Paul Warren, Emily A Wrona, Matthew B Fisher, Donald O Freytes
Inflammation is an essential component of the normal mammalian host tissue response and plays an important role during cardiovascular and musculoskeletal diseases. Given the important role of inflammation on the host tissue response after injury, understanding this process represents essential aspects of biomedical research, tissue engineering, and regenerative medicine. Macrophages are central players during the inflammatory response with an extensive role during wound healing. These cells exhibit a spectrum of activation states that span from pro-inflammatory to pro-healing phenotypes...
2017: Results and Problems in Cell Differentiation
Svenja F B Mennens, Koen van den Dries, Alessandra Cambi
Tissue homeostasis is not only controlled by biochemical signals but also through mechanical forces that act on cells. Yet, while it has long been known that biochemical signals have profound effects on cell biology, the importance of mechanical forces has only been recognized much more recently. The types of mechanical stress that cells experience include stretch, compression, and shear stress, which are mainly induced by the extracellular matrix, cell-cell contacts, and fluid flow. Importantly, macroscale tissue deformation through stretch or compression also affects cellular function...
2017: Results and Problems in Cell Differentiation
Martin Lee, Kevin Rey, Katrina Besler, Christine Wang, Jonathan Choy
Nitric oxide (NO) is a bioactive gas that has multiple roles in innate and adaptive immune responses. In macrophages, nitric oxide is produced by inducible nitric oxide synthase upon microbial and cytokine stimulation. It is needed for host defense against pathogens and for immune regulation. This review will summarize the role of NO and iNOS in inflammatory and immune responses and will discuss the regulatory mechanisms that control inducible nitric oxide synthase expression and activity.
2017: Results and Problems in Cell Differentiation
Alexandra Dos Anjos Cassado
Tissue macrophages are a heterogeneous cell population residing in all body tissues that contribute to the maintenance of homeostasis and trigger immune activation in response to injurious stimuli. This heterogeneity may be associated with tissue-specific functions; however, the presence of distinct macrophage populations within the same microenvironment indicates that macrophage heterogeneity may also be influenced outside of tissue specialization. The F4/80 molecule was established as a unique marker of murine macrophages when a monoclonal antibody was found to recognize an antigen exclusively expressed by these cells...
2017: Results and Problems in Cell Differentiation
Prasad Abnave, Xavier Muracciole, Eric Ghigo
Macrophages are critical components of the antimicrobial response. The recent explosion of knowledge on the evolutionary, genetic, and biochemical aspects of the interaction between macrophages and microbes has renewed scientific interest in macrophages. The conservation of immune components or mechanisms between organisms during the evolutionary process allows us to elucidate antimicrobial mechanisms or discover new immune functions through the study of basal-branching organisms, such as invertebrates. As a result, immunity in non-vertebrates has attracted the attention of researchers in the last few decades...
2017: Results and Problems in Cell Differentiation
Elżbieta Wałajtys-Rode, Jolanta M Dzik
Monocyte/macrophage and natural killer (NK) cells are partners from a phylogenetic standpoint of innate immune system development and its evolutionary progressive interaction with adaptive immunity. The equally conservative ways of development and differentiation of both invertebrate hemocytes and vertebrate macrophages are reviewed. Evolutionary conserved molecules occurring in macrophage receptors and effectors have been inherited by vertebrates after their common ancestor with invertebrates. Cytolytic functions of mammalian NK cells, which are rooted in immune cells of invertebrates, although certain NK cell receptors (NKRs) are mammalian new events, are characterized...
2017: Results and Problems in Cell Differentiation
Patricia Luz-Crawford, Christian Jorgensen, Farida Djouad
Mesenchymal stem cells (MSC) are multipotent stem cells with a broad well-described immunosuppressive potential. They are able to modulate both the innate and the adaptive immune response. Particularly, MSC are able to regulate the phenotype and function of macrophages that are critical for different biological processes including wound healing, inflammation, pathogenesis of several autoimmune diseases, and tumor growth. These multifunctional roles of macrophages are due to their high plasticity, which enable them to adopt different phenotypes such as a pro-inflammatory M1 and anti-inflammatory M2 phenotype...
2017: Results and Problems in Cell Differentiation
Leticia Reyes, Bryce Wolfe, Thaddeus Golos
Pregnancy complications such as preterm birth, miscarriage, maternal and/or neonatal morbidities, and mortality can be manifestations of underlying placental pathology. Hofbauer cells refer to a heterogeneous population of fetal macrophages that reside within the functional unit of the placenta known as the chorionic villus. Hofbauer cells can be detected within the connective tissue matrix of the placenta as early as 4 weeks post-conception and are present throughout pregnancy. These cells are implicated in a wide array of functions important for a successful pregnancy including placental morphogenesis, immune regulation, control of stromal water content, and the transfer of ions and serum proteins across the maternal-fetal barrier...
2017: Results and Problems in Cell Differentiation
Paola Italiani, Diana Boraschi
Mononuclear phagocytes are key cells in tissue integrity and defense. Tissue-resident macrophages are abundantly present in all tissues of the body and have a complex role in ensuring tissue functions and homeostatic balance. Circulating blood monocytes can enter tissue both in steady-state conditions, for helping in replenishing the tissue-resident macrophage pool and, in particular, for acting as potent effector cells during inflammatory events such as infections, traumas, and diseases. The heterogeneity of monocytes and macrophages depends on their ontogeny, their tissue location, and their functional programming, with both monocytes and macrophages able to exert distinct or similar functions depending on the tissue-specific and stimulus-specific microenvironment...
2017: Results and Problems in Cell Differentiation
Eva-Stina Edholm, Kun Hyoe Rhoo, Jacques Robert
Macrophages constitute a heterogeneous population of myeloid cells that are essential for maintaining homeostasis and as a first line of innate responders controlling and organizing host defenses against pathogens. Monocyte-macrophage lineage cells are among the most functionally diverse and plastic cells of the immune system. They undergo specific activation into functionally distinct phenotypes in response to immune signals and microbial products. In mammals, macrophage functional heterogeneity is defined by two activation states, M1 and M2, which represent two polar ends of a continuum exhibiting pro-inflammatory and tissue repair activities, respectively...
2017: Results and Problems in Cell Differentiation
Ana S Cruz-Solbes, Keith Youker
Tubulointerstitial injury is one of the hallmarks of renal disease. In particular, interstitial fibrosis has a prominent role in the development and progression of kidney injury. Collagen-producing fibroblasts are responsible for the ECM deposition. However, the origin of those activated fibroblasts is not clear. This chapter will discuss in detail the concept of epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT) in the context of fibrosis and kidney disease. In short, EMT and EndMT involve a change in cell shape, loss of polarity and increased motility associated with increased collagen production...
2017: Results and Problems in Cell Differentiation
Cheng Jack Song, Kurt A Zimmerman, Scott J Henke, Bradley K Yoder
Polycystic kidney disease (PKD) is a commonly inherited disorder characterized by cyst formation and fibrosis (Wilson, N Engl J Med 350:151-164, 2004) and is caused by mutations in cilia or cilia-related proteins, such as polycystin 1 or 2 (Oh and Katsanis, Development 139:443-448, 2012; Kotsis et al., Nephrol Dial Transplant 28:518-526, 2013). A major pathological feature of PKD is the development of interstitial inflammation and fibrosis with an associated accumulation of inflammatory cells (Grantham, N Engl J Med 359:1477-1485, 2008; Zeier et al...
2017: Results and Problems in Cell Differentiation
Prachee Avasthi, Robin L Maser, Pamela V Tran
Primary cilia are small, antenna-like structures that detect mechanical and chemical cues and transduce extracellular signals. While mammalian primary cilia were first reported in the late 1800s, scientific interest in these sensory organelles has burgeoned since the beginning of the twenty-first century with recognition that primary cilia are essential to human health. Among the most common clinical manifestations of ciliary dysfunction are renal cysts. The molecular mechanisms underlying renal cystogenesis are complex, involving multiple aberrant cellular processes and signaling pathways, while initiating molecular events remain undefined...
2017: Results and Problems in Cell Differentiation
Abhijeet Pal, Kimberly J Reidy
Renal anomalies are common birth defects that may manifest as a wide spectrum of anomalies from hydronephrosis (dilation of the renal pelvis and calyces) to renal aplasia (complete absence of the kidney(s)). Aneuploidies and mosaicisms are the most common syndromes associated with CAKUT. Syndromes with single gene and renal developmental defects are less common but have facilitated insight into the mechanism of renal and other organ development. Analysis of underlying genetic mutations with transgenic and mutant mice has also led to advances in our understanding of mechanisms of renal development...
2017: Results and Problems in Cell Differentiation
Kieran M Short, Ian M Smyth
The kidney develops as an outgrowth of the epithelial nephric duct known as the ureteric bud, in a position specified by a range of rostral and caudal factors which serve to ensure two kidneys form in the appropriate positions in the body. At its simplest level, kidney development can be viewed as the process by which this single bud then undergoes a process of arborisation to form a complex connected network of ducts which will serve to drain urine from the nephrons in the adult organ. The process of bud elaboration is dictated by factors expressed by both the bud itself and by surrounding cells of the metanephric mesenchyme which control cell division and bifurcation...
2017: Results and Problems in Cell Differentiation
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