Langerhans cells--their structure, function and pathological role

Data on the structure and function of Langerhans' cells (LC) are presented. LC are defined as dendritic cells of the epidermis and mucous membrane epithelium having the mesenchymal origin and relating to the antigen-representing macrophages. Morphological, enzymatic and antigenic LC markers are characterized. The crucial role of LC in the development of the skin delayed type hypersensitivity is shown: contact hypersensitivity, specific inflammation, transplant rejection, neoplastic process.     

ABC transporters: physiology, structure and mechanism--an overview.

ABC transporters form one of the largest of all protein families with a diversity of physiological functions. In Escherichia coli almost 5% of the genome is occupied by genes encoding components of these transporters, and there are examples in all species from microbes to man. In this overview, the importance of studies on bacteria in elucidating many basic principles pertaining to ABC transporters is emphasised. The family is described and a general overview of the structure and function of these transporters is presented.     

Aldosterone-regulated ion transporters in the kidney

Summary Madin-Darby canine kidney (MDCK) cells resemble intercalated cells of the renal collecting duct. In these cultured epithelial cells aldosterone activates apical Na⁺/H⁺ exchange, initiating a cascade of intracellular events such as cell growth, epithelial cell polarity, and stimulation of transepithelial ion transport. Transepithelial K⁺ secretion is triggered by the insertion of new ion channels and the activation of previously quiescent channels with increasing cytoplasmic pH. Aldosterone supplies the cell with ion transporters necessary for adequate function of the renal collecting duct when the organism is metabolically challenged.     

Xanthogranulomatous mastitis: Clinicopathology and pathological implications

Xanthogranulomatous inflammation is an uncommon finding in the breast. Sixteen cases of xanthogranulomatous mastitis were reviewed to determine the characteristic clinicopathological features. Xanthogranulomatous mastitis involved foamy histiocyte clusters interspersed with inflammatory cells. Foamy histiocytes were bland with small pyknotic nuclei. Xanthogranulomatous mastitis was associated with fat necrosis in five cases (31%), multinucleated giant-cell reactions in six cases (38%), and cholesterol crystals in five cases (31%). In three cases (19%), xanthogranulomatous mastitis coincided with ductal carcinoma in situ or invasive ductal carcinoma. Duct ectasia with foamy histiocyte aggregates were noted in five cases (31%). It is suggested that the etiology of xanthogranulomatous mastitis is obstruction and rupture of the ectatic duct with foamy histiocyte aggregates. In breast core biopsy, granular cell tumor and invasive carcinoma such as histiocytoid carcinoma and lipid-rich carcinoma could demonstrate similar pathological features to xanthogranulomatous mastitis. In conclusion, xanthogranulomatous mastitis could be encountered in breast core biopsy and surgical excision tissue. Diagnosis of xanthogranulomatous mastitis can be made by excluding other diseases that elicit xanthogranulomatous inflammation in the breast. In breast core biopsy, xanthogranulomatous mastitis could be distinguished from granular cell tumor, histiocytoid carcinoma and lipid-rich carcinoma by using cytokeratin and histiocytic marker such as α1-anti-trypsin and CD68 stain.     

Angiogenesis in the female reproductive organs: pathological implications

The female reproductive organs (ovary, uterus, and placenta) are some of the few adult tissues that exhibit regular intervals of rapid growth. They also are highly vascular and have high rates of blood flow. Angiogenesis, or vascular growth, is therefore an important component of the growth and function of these tissues. As with many other tissues, vascular endothelial growth factors (VEGFs) and fibroblast growth factors (FGFs) appear to be major angiogenic factors in the female reproductive organs. A variety of pathologies of the female reproductive organs are associated with disturbances of the angiogenic process, including dysfunctional uterine bleeding, endometrial hyperplasia and carcinoma, endometriosis, failed implantation and subnormal foetal growth, myometrial fibroids (uterine leiomyomas) and adenomyosis, ovarian hyperstimulation syndrome, ovarian carcinoma, and polycystic ovary syndrome. These pathologies are also associated with altered expression of VEGFs and/or FGFs. In the near future, angiogenic or antiangiogenic compounds may prove to be effective therapeutic agents for treating these pathologies. In addition, monitoring of angiogenesis or angiogenic factor expression may provide a means of assessing the efficacy of these therapies.     

The structure and ligand interactions of CD2: implications for T-cell function

Considerable progress has recently been made in understanding the structure and ligand interactions of the T-cell antigen CD2, to the extent that CD2 is now a useful paradigm for considering the structural basis of cell-cell recognition. Here, Simon Davis and Anton van der Merwe review the new data and consider their implications for T-cell function in the context of CD2-knockout experiments.     

Perforin: structure,function, and role in human immunopathology

Summary: The secretory granule-mediated cell death pathway is the key mechanism for elimination of virus-infected and transformed target cells by cytotoxic lymphocytes. The formation of the immunological synapse between an effector and a target cell leads to exocytic trafficking of the secretory granules and the release of their contents, which include pro-apoptotic serine proteases, granzymes, and pore-forming perforin into the synapse. There, perforin polymerizes and forms a transmembrane pore that allows the delivery of granzymes into the cytosol, where they initiate various apoptotic death pathways. Unlike relatively redundant individual granzymes, functional perforin is absolutely essential for cytotoxic lymphocyte function and immune regulation in the host. Nevertheless, perforin is still the least studied and understood cytotoxic molecule in the immune system. In this review, we discuss the current state of affairs in the perforin field: the protein’s structure and function as well as its role in immune-mediated diseases.     

Neocortical neuron types in Xenarthra and Afrotheria: implications for brain evolution in mammals

Interpreting the evolution of neuronal types in the cerebral cortex of mammals requires information from a diversity of species. However, there is currently a paucity of data from the Xenarthra and Afrotheria, two major phylogenetic groups that diverged close to the base of the eutherian mammal adaptive radiation. In this study, we used immunohistochemistry to examine the distribution and morphology of neocortical neurons stained for nonphosphorylated neurofilament protein, calbindin, calretinin, parvalbumin, and neuropeptide Y in three xenarthran species—the giant anteater (Myrmecophaga tridactyla), the lesser anteater (Tamandua tetradactyla), and the two-toed sloth (Choloepus didactylus)—and two afrotherian species—the rock hyrax (Procavia capensis) and the black and rufous giant elephant shrew (Rhynchocyon petersi). We also studied the distribution and morphology of astrocytes using glial fibrillary acidic protein as a marker. In all of these species, nonphosphorylated neurofilament protein-immunoreactive neurons predominated in layer V. These neurons exhibited diverse morphologies with regional variation. Specifically, high proportions of atypical neurofilament-enriched neuron classes were observed, including extraverted neurons, inverted pyramidal neurons, fusiform neurons, and other multipolar types. In addition, many projection neurons in layers II–III were found to contain calbindin. Among interneurons, parvalbumin- and calbindin-expressing cells were generally denser compared to calretinin-immunoreactive cells. We traced the evolution of certain cortical architectural traits using phylogenetic analysis. Based on our reconstruction of character evolution, we found that the living xenarthrans and afrotherians show many similarities to the stem eutherian mammal, whereas other eutherian lineages display a greater number of derived traits.     

Neutrophil trafficking to lymphoid tissues: physiological and pathological implications

Recent advances have provided evidence for the involvement of neutrophils in both innate and adaptive immunity, robustly challenging the old dogma that neutrophils are short-lived prototypical innate immune cells solely involved in acute responses to microbes and exerting collateral tissue damage. There is now ample evidence showing that neutrophils can migrate into different compartments of the lymphoid system where they contribute to the orchestration of the activation and/or suppression of lymphocyte effector functions in homeostasis and during chronic inflammation, such as autoimmune disorders and cancer. In support of this notion, neutrophils can generate a wide range of cytokines and other mediators capable of regulating the survival, proliferation and functions of both T and B cells. In addition, neutrophils can directly engage with lymphocytes and promote antigen presentation. Furthermore, there is emerging evidence of the existence of distinct and diverse neutrophil phenotypes with immunomodulatory functions that characterise different pathological conditions, including chronic and autoimmune inflammatory conditions. The aim of this review is to discuss the mechanisms implicated in neutrophil trafficking into the lymphoid system and to provide an overview of the immuno-regulatory functions of neutrophils in health and disease in the context of adaptive immunity. Copyright © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Genetic evolution of enterovirus 71: epidemiological and pathological implications

Since its discovery in the 1970s, enterovirus 71 (EV71) has become one of the most pathogenic enterovirus serotypes causing recurrent outbreaks in different parts of the world. Three waves of outbreaks globally have been recorded over the last three decades and more recently active circulation of EV71 is evident amongst countries in South East Asia and beyond. There is evidence of a continuous evolution in its genetic make up which is likely to impact on its epidemiology and pathological potential. This review examines the molecular genetics and evolution of EV71 in relation to its epidemiological and pathological properties. A thorough understanding of the relationship between the genetic changes and the resulting host-virus interaction is essential for successful control.     

Seasonal variations in the fine structure of the Necturus maculosus urinary bladder epithelium: Low transporters and high transporters

Although the urinary bladder of Necturus maculosus provides an important model system for studying the mechanisms of active Na absorption, little critical attention has been paid to the fine structure of its epithelium. Moreover, two distinct groups of urinary bladders, low and high Na transporters, have been described based on short-circuit current or transepithelial potential difference. In the present study, over an 11-month period, stable electrical parameters (short-circuit current, transepithelial potential difference, and resistance) were recorded from 63 chamber-mounted bladders. Analysis of these parameters revealed a highly significant difference between two groups (low transporters and high transporters) occurring at different times of the year. Consistent with these data, in urine collected from the bladders, the Na concentration in low transporters was significantly higher than that in high transporters. A subpopulation of these bladders was subsequently fixed and examined at the light and/or electron microscopic level. Low-transporting bladders were characterized unequivocally by a thin, stratified squamous epithelium only 6–15 μm thick. High-transporting bladders were composed predominantly of columnar-shaped granular cells up to 70 μm in height, with ciliated, mitochondria-rich, and basal cells present in small numbers. There is thus a correlation between transport activity, as measured by electrophysiological techniques and urine sodium analysis, and the structure of the tissue. Moreover, these parameters exhibit significant seasonal variation, the underlying mechanisms of which remain obscure.     

Na-coupled bicarbonate transporters of the solute carrier 4 family in the nervous system: function, localization, and relevance to neurologic function

Many cellular processes including neuronal activity are sensitive to changes in intracellular and/or extracellular pH-both of which are regulated by acid-base transporter activity. HCO(3)(-)-dependent transporters are particularly potent regulators of intracellular pH in neurons and astrocytes, and also contribute to the composition of the cerebrospinal fluid (CSF). The molecular physiology of HCO(3)(-) transporters has advanced considerably over the past ～14 years as investigators have cloned and characterized the function and localization of many Na-Coupled Bicarbonate Transporters of the solute carrier 4 (Slc4) family (NCBTs). In this review, we provide an updated overview of the function and localization of NCBTs in the nervous system. Multiple NCBTs are expressed in neurons and astrocytes in various brain regions, as well as in epithelial cells of the choroid plexus. Characteristics of human patients with SLC4 gene mutations/deletions and results from recent studies on mice with Slc4 gene disruptions highlight the functional importance of NCBTs in neuronal activity, somatosensory function, and CSF production. Furthermore, energy-deficient states (e.g., hypoxia and ischemia) lead to altered expression and activity of NCBTs. Thus, recent studies expand our understanding of the role of NCBTs in regulating the pH and ionic composition of the nervous system that can modulate neuronal activity.     

Iliocostalis muscles in three mammals (dolphin,goat and human): Their identification,structure and innervation

Iliocostalis (IC) muscles were studied in four dolphin embryos, three goat embryos and four Japanese adult cadavers through macroscopic dissection. The IC muscles of the dolphin were located on the lateral aspect of the trunk and displayed an intercostal arrangement. In contrast, the IC muscles in both the goat and human showed a double-layered architecture formed by a multisegmental muscle-tendon complex and were located on the lateral and medial sides of the costal angle, respectively. Generally, the nerve to the iliocostalis (NIC) in the dolphin and goat did not form a common trunk with the nerve to the longissimus on the epaxial plane, whereas in humans the NIC ran parallel to the nerve to the longissimus part of the way. The individual NIC ran caudolaterally, innervating the one lower (caudal) metameric division of the IC muscle in the dolphin and piercing the fascia of the IC muscles at a point in the next caudal intercostal level in the goat and human. In the upper thoracic part of the goat and human, the caudal shift of innervation was obscured, where the IC muscles were close to the vertebrae. The course of the NIC was closely related to that of the lateral cutaneous branch. The present study shows that the NIC is commonly destined for the one lower intercostal level among the three mammalian species, with their respective IC muscles having distinctly different structural complexity.