Differentiation of regenerating pancreatic cells into hepatocyte-like cells.

Differentiation is the process by which multicellular organisms achieve the specialized functions necessary for adaptation and survival. An in vivo model in the Syrian golden hamster is described in which regenerating pancreatic cells are converted into hepatocyte-like cells, as evidenced by the presence of albumin, peroxisomes, and a variety of morphological markers. These cells are stable after the conversion is triggered by a single dose of the carcinogen N-nitrosobis(2-oxopropyl)amine administered during the S phase in regenerating pancreatic cells. This suggests that, given the proper stimulus, regenerating cells in adult pancreas can be redirected into a totally different pathway of differentiation.     

Dendritic cells: ontogeny.

Dendritic cells (DC) play key rolls in various aspects of immunity. The functions of DC depend on the subsets as well as their location or activation status. Understanding developmental lineages, precursors and inducing factors for various DC subsets would help their clinical application, but despite extensive efforts, the precise ontogeny of various DC, remain unclear and complex. Because of their many functional similarities to macrophages, DC were originally thought to be of myeloid-lineage, an idea supported by many in vitro studies where monocytes or GM-CSF (a key myeloid growth factor) has been extensively used for generating DC. However, there has been considerable evidence which suggests the existence of lymphoid-lineage DC. After the confusion of myeloid-/lymphoid-DC concept regarding DC surface markers, we have now reached a consensus that each DC subset can differentiate through both myeloid- and lymphoid-lineages. The identification of committed populations (such as common myeloid- and lymphoid progenitors) as precursors for every DC subsets and findings from various knockout (KO) mice that have selected lymphoid- or myeloid-lineage deficiency appear to indicate flexibility of DC development rather than their lineage restriction. Why is DC development so flexible unlike other hematopoitic cells? It might be because there is developmental redundancy to maintain such important populations in any occasions, or such developmental flexibility would be advantageous for DC to be able to differentiate from any “available” precursors in situ irrespective of their lineages. This review will cover ontogeny of conventional (CD8 +/- DC) DC, plasmacytoid DC and skin Langerhans cells, and recently-identified many Pre-DC (immediate DC precursor) populations, in addition to monocytes and plasmacytoid DC, will also be discussed.     

Antihistamines and epithelial cells.

Antihistamines have long been utilized in the symptomatic management (antihistaminic effects) of allergic rhinitis and conjunctivitis. Investigation into the nonsedating second-generation antihistamines suggests that they also possess antiinflammatory activity, and may be useful in the management of inflammation associated with allergic airway disease. In vitro studies have shown that these antihistamines decrease the migration and activation of eosinophils and diminish the release of pro-inflammatory mediators from mast cells and basophils after induction by immunological and nonimmunological stimuli. In vivo studies have also demonstrated that these antihistamines decrease inflammatory cell infiltration in allergic airway disease, and mediator release from mast cells and basophils. Epithelial cells, due to their spatial arrangement and predominance in the airways, play a pivotal role in the etiology of airway disease. There is evidence that antihistamines may modulate airway inflammation by influencing the activity of these airway epithelial cells. Studies have shown that expression of adhesion molecules on epithelial cells is decreased by second-generation antihistamines. Collectively, these studies suggest that second-generation H1-histamine receptor antagonists have potential use either as safe antiinflammatory alternatives to corticosteroids or as rescue medication in combination with corticosteroids for the management of severe airway disease.     

Glicentin immunoreactive cells: their relationship to glucagon-producing cells.

The cellular and subcellular localization of one of the gut glucagon-like immunoreactants (GLI-1 or glicentin) and the relative distribution of glicentin- and glucagon-containing cells were investigated by immunocytochemistry. By immunofluorescence, the antiglicentin serum, which does not react with glucagon, revealed positive cells in the islets of Langerhans and in the gut mucosa, particularly in the terminal ileum and colon. In the intestinal mucosa, it was proven ultrastructurally that the glicentin immunoreactive cells correspond to the L cell and that the secretory granules represent the storage compartment of the immunoreactive material. In pancreatic islets, consecutive semithin sections treated with antiglicentin and specific antiglucagon sera showed that the same A cell population reacted with both sera, while immunoperoxidase staining on thin sections revealed that the immunoreactive material was confined to the secretory granules. The same results were obtained on dog oxyntic mucosa, where the glicentin- and glucagon-containing cells were identified as the gastric A cell. The immunocytochemical demonstration of a common glicentin-like material in the A and L cells together with the known presence of a common immunoreactant in glicentin and glucagon strongly support the idea that the A and L cells are ontogenetically related and synthesize their secretory product via a glicentin-like precursor which, by specific cleavage, could yield glucagon and gut glucagon-like immunoreactants.     

Trout steroidogenic testicular cells in primary culture. II. Steroidogenic activity of interstitial cells, Sertoli cells, and spermatozoa

Somatic cells (interstitial cells and Sertoli cells) were prepared either as single cells or in clusters, from spermatogenic and mature trout testes, according to Loir (1988), and cultured for 10-14 days. Sertoli cells are 3 beta-HSD negative when prepared from testes resuming spermatogenesis and from mature testes, but they are 3 beta-HSD positive in spermatogenic testes. Progesterone, 17 alpha-hydroxyprogesterone (17 alpha-OH-P), and free androgens are secreted by interstitial cells, 11-ketotestosterone (11KT) being the predominating steroid produced immediately after seeding. These cells also produce high levels of glucuronated androgens. At least in mature spermiating testes they do not secrete estradiol. After isolation, interstitial cells would lose most of their ability to secrete 17 alpha-hydroxy,20 beta-dihydroprogesterone (17 alpha 20 beta-OH-P) but they would recover it later. Testicular spermatozoa, which convert 17 alpha-OH-P independently of s-GtH, constitute a second source of this progestagen. In addition, our results suggest that Sertoli cells could be able to secrete 17 alpha-OH-P and also progesterone. A possible participation of the intralobular production of the former progestagen to the local regulation of germ cell maturation is evoked.     

Transport of ferritin from Kupffer cells to liver parenchymal cells. Morphological and immunocytochemical observations.

In attempting to determine the pathway of ferritin from Kupffer cells to liver parenchymal cells, anionic iron colloid particles of a ferric hydroxide-potassium polyvinyl sulfate complex (Fe-PVS) were injected intravenously into blood-depleted anemic rats. After iron loading, the process of ferritin formation and the daily change in the latter's distribution in the liver were studied by ultrastructural-immunocytochemical techniques. Three days after Fe-PVS injection, a mass of reaction products of ferritin was found in Kupffer cells, though not in the sinusoidal endothelial or parenchymal cells. Four days post-Fe-PVS injection, however, reaction products in Kupffer cells disappeared, while appearing in parenchymal cells. Observations at 3.5 days after the injection revealed heavy deposition of reaction products in the sinusoid and Disse's spaces as well. Electron microscopic observation of tissue sections treated with bismuth subnitrate taken at this stage revealed diffuse dispersion of ferritin particles in the cytoplasmic matrix of parenchymal cells as well as in the sinusoid and Disse's spaces. Ferritin particles were not found in the coated pits and vesicles of the Kupffer cells and parenchymal cells. Four days after injection, ferritin particles were found in clusters in the cytoplasm of the parenchymal cells and also in their lysosomal bodies. The results indicate that ferritin synthesized in Kupffer cells is released into sinusoidal and Disse's spaces and then accumulated in parenchymal cells.     

Blood cells diseases and thrombosis.

BACKGROUND AND OBJECTIVES: In recent years knowledge about thrombophilia and the mechanisms underlying the pathogenesis of thrombosis has increased greatly. Nevertheless the role of leukocytes and red cells in thrombogenesis is not well established and is probably underestimated. EVIDENCE AND INFORMATION SOURCES: The contribution of leukocytes and red cells to thrombogenesis has been reviewed. Moreover, the prevalence of thrombosis as a complication of hematologic diseases has been examined. The authors are involved in the investigation and management of acute and chronic hematologic diseases as well as in investigation of thrombophilia. Pub-Med was employed as a source of information. STATE OF THE ART: Thrombosis is a major problem in myeloproliferative disorders such as polycythemia vera and essential thrombocythemia. A clonal involvement of megakaryocytopoiesis resulting in elevated levels of platelet-specific proteins, increased thromboxane generation, and expression of activation-dependent epitopes on the platelet surface is regarded as the main origin of thromboembolism; nevertheless, activation of leukocytes and the consequent release of elastase and alkaline phosphatase could play an important role, determining endothelial damage. Thrombosis is a relevant problem in some hemolytic anemias such as paroxysmal nocturnal hemoglobinuria and drepanocytosis. Thrombotic events in hemolytic anemias with membrane defects have been attributed, at least in part, to hypercoagulability related to the exposure of phosphatidylserine of red cell membrane activating plasma prothrombinase and supplying a procoagulant phospholipid anionic surface. A moderate but well-established risk for thrombosis occurs in acute promyelocytic leukemia and acute lymphoblastic leukemia; this risk could be increased by antiblastic drugs affecting the procoagulant activity of cells and the production of coagulation inhibitors from the liver. PERSPECTIVES: Thrombotic complications during hematologic diseases other than thrombophilia due to plasma alteration could be decreased not only by anticoagulant and antiaggregating agents but also by drugs inhibiting activation of leukocytes and red cells and their interaction with platelets.     

Pit cells in the liver.

There is now sufficient evidence to consider the pit cells as a hepatic, intrasinusoidal population of large granular lymphocytes. They should be considered as resident sinusoidal cells of the liver, even if they depend on a continuous influx of precursor cells from the bone marrow, since they differ in several phenotypic and functional respects from their circulating (precursor) counterparts. There is growing evidence that a comparable population of activated or further differentiated, liver-specific pit cells (or LGL) is not only present in the rat but also in the human liver. Pit cells exert high spontaneous cytotoxic activity against tumor cell lines and may act as a primary defense barrier to metastasizing tumor cells and to virus infections. The total number of pit cells in the liver can be greatly increased by the administration of interleukin-2 or by a variety of biological response modifiers, which may represent a mechanism of defense against disease. Their involvement in liver pathologies deserves more attention.     

Prolactin production by immune cells.

Prolactin (PRL) is a pituitary hormone and a cytokine that plays an important role in rodent and human immune responses, including autoimmune diseases. However, many cells and tissues other than the pituitary make PRL, including immune cells. Here, we will present the evidence demonstrating PRL synthesis by different subtypes of immune cells from humans, mice and rats, describe the regulation of PRL gene expression in human lymphocytes, and discuss the functions of PRL made by immune cells. Finally, we will present evidence for involvement of immune cell PRL in human autoimmune disease and suggest how it might play a unique immunoregulatory role.