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PubMedDate not supplied

Intestinal secretion of IgA and IgM: a hypothetical model.

The secretory component (SC) has recently been found to be associated with IgM in external secretions, although in a less stable complex than secretory IgA. Moreover, SC combines spontaneously in vitro with both IgA and IgM. A prerequisite is that the immunoglobulins contain the J chain, which is present only in dimers and polymers. This polypeptide is essential for the formation of an SC-binding site which appears already at the cytoplasmic level in IgA- and IgM-producing immunocytes. Locally formed J-chain-containing immunoglobulins are therefore readily available for complexing with SC present in the membranes of columnar secretory epithelial cells of glandular sites. This complexing initiates pinocytosis and external transport. Immunohistochemically the gland cells are shown to contain SC, IgA and IgM in identical locations, except that SC alone appears in the Golgi zone. Locally formed IgA and IgM antibodies are thus efficiently transferred to the mucosal surface where they exert an immunological exclusion of antigens. Conversely, IgG antibodies, which are not actively drained away from the lamina propria, may rather become engaged in complement activation and cell-mediated cytotoxicity with potentially deleterious effects on the tissue. Secondary to severe inflammatory reactions, secretory epithelium may show decreased production of SC; the selective external transport of SC-stabilized secretory IgA and IgM is thus jeopardized, and a vicious circle may be set up in the mucosa.

Animals↗
PubMed1988

Ultrastructure of the pineal body of the common vampire bat, Desmodus rotundus.

The type AB pineal body of the common vampire bat, Desmodus rotundus, was recessed and lobulated, was extensively vascularized and intimately related to great veins, and was unassociated with the epithalamic region. The habenular and the posterior commissures coursed anteriorly and were unassociated with the pineal. The saccular suprapineal recess of the third ventricle extended dorsally juxtaposed to the pineal body. These anatomical features are likely to make pinealectomies in the vampire more difficult to manage. The pineal parenchyma consisted of light pinealocytes surrounded by canaliculi of various sizes, often transmitting unmyelinated nerve fibers and glial processes. Desmosomes were common. The pinealocyte nuclei were large and highly infolded; characteristic cytoplasmic constituents included abundant dilated Golgi complexes associated with clear vesicles, numerous polyribosomes, few single cisternae of ribosome-studded rough endoplasmic reticulum, mitochondria, and occasional multivesicular bodies and lysosomes. Almost all pinealocytes exhibited centrioles and some, in addition, displayed basal bodies but rarely ciliary shafts. A conspicuous feature of the pinealocyte cytoplasm was the presence of branched bundles of intermediate filaments, especially in the perinuclear zone. Siderotic macrophages, lipofuscin-pigment-containing phagocytic cells, mast cells, myelin bodies, and both fenestrated and continuous capillaries were present. The perivascular compartment was densely packed with unmyelinated nerve bundles containing small to large fibers exhibiting axoaxonic densities. Other constituents of the perivascular compartment were club-shaped pinealocyte processes filled with clear vesicles, microtubules, an occasional mitochondrion, glial processes, and collagen fibers. "Synapselike" contacts were observed between the axons and pinealocyte processes. Abundant pinocytotic vesicles in the capillary endothelium indicated active pinocytosis. Myelinated nerve fibers were lacking. The pineal ultrastructure of Desmodus is in part unlike that reported for other mammals, including bats.

Animals↗
PubMed1979

Structure and function of the intestinal epithelial cells in the perch (Perca fluviatillis L.).

An ultrastructural study of the intestinal absorptive epithelium in perch (Perca fluviatilis) has shown that the perch intestine can be divided into three segments: the proximal segment, the middle segment and the distal segment. The enterocytes of the proximal segment are found to be concerned with lipid absorption. The adsorbed fat gives rise to the presence of two forms of inclusions: lipid particles and lipid droplets. Enterocytes of the middle segment exhibit the typical ultrastructural features of pinocytosis; these consist of extensive invaginations of the luminal surface membrane and acculation of vacuoles in the apical cytoplasm. Exogenous proteins are ingested by absorptive cells from the intestinal lumen by a process similar to that described in neonatal mammals. In the distal segment the absorptive cells have few, short microvilli. Besides the absorptive epithelial cells, goblet cells, endocrine cells, pear-shaped cells, and plasma cells are occasionally found.

Animals↗
PubMed1980

Serous cysts of the aging guinea pig ovary. III. Permeability of the cyst epithelium to lanthanum and horseradish peroxidase.

The permeability of the epithelium lining serous cysts of the guinea pig ovary was examined using lanthanum and horseradish peroxidase (HRP). Both lanthanum and HRP introduced at the luminal surface of the cyst penetrated to the basal region filling caveolae in both lateral and basal cell surfaces. Within three minutes of vascular infusion of HRP, the tracer was detected between epithelial cells and in caveolae on their lateral and basal surfaces but not associated with intracellular organelles. There was no change in the intracellular distribution of HRP after ten minutes. It was concluded that the epithelium was permeable to the tracers within this time period but that pinocytosis and transport of these tracers through the epithelial cell were not demonstrated.

Aging↗
PubMed1990

Synthesis and transport of storage proteins by testes in Heliothis virescens.

The synthesis of two storage protein subunits, 76,000-Mr and 82,000-Mr polypeptides, by the testes sheath has been studied in Heliothis virescens. Like fat body, which is the primary site of synthesis for the large extratesticular pool, cells of the testes sheath secrete glycosylated storage proteins assembled into hexamers. The testis sheath differed from fat body in several important respects, including the failure to synthesize an abundant (in the hemolymph) 74,000-Mr storage protein, its relatively reduced expression of the 76,000-Mr polypeptide, and the absence of resorption of storage proteins from the lumen of the testis during pupal development. Cyst cells were also shown to import actively the 82,000-Mr storage protein by pinocytosis of testicular fluid and transfer it to the developing spermatids. Unlike other cell types that sequester storage proteins in the form of cytoplasmic granules, their localization within spermatids was exclusively mitochondrial. These observations suggest that expression of the storage protein genes is regulated tissue specifically and reveal novel pathways for their transport and, perhaps, utilization and function during development.

Animals↗
PubMed2004

Mechanisms regulating toxicant disposition to the embryo during early pregnancy: an interspecies comparison.

The dose of toxicant reaching the embryo is a critical determinant of developmental toxicity, and is likely to be a key factor responsible for interspecies variability in response to many test agents. This review compares the mechanisms regulating disposition of toxicants from the maternal circulation to the embryo during organogenesis in humans and the two species used predominantly in regulatory developmental toxicity testing, rats and rabbits. These three species utilize fundamentally different strategies for maternal-embryonic exchange during early pregnancy. Early postimplantation rat embryos rely on the inverted visceral yolk sac placenta, which is in intimate contact with the uterine epithelium and is equipped with an extensive repertoire of transport mechanisms, such as pinocytosis, endocytosis, and specific transporter proteins. Also, the rat yolk sac completely surrounds the embryo, such that the fluid-filled exocoelom survives through most of the period of organogenesis, and can concentrate compounds such as certain weak acids due to pH differences between maternal blood and exocelomic fluid. The early postimplantation rabbit conceptus differs from the rat in that the yolk sac is not closely apposed to the uterus during early organogenesis and does not completely enclose the embryo until relatively later in development (approximately GD13). This suggests that the early rabbit yolk sac might be a relatively inefficient transporter, a conclusion supported by limited data with ethylene glycol and one of its predominant metabolites, glycolic acid, given to GD9 rabbits. In humans, maternal-embryo exchange is thought to occur via the chorioallantoic placenta, although it has recently been conjectured that a supplemental route of transfer could occur via absorption into the yolk sac. Knowledge of the mechanisms underlying species-specific embryonic disposition, factored together with other pharmacokinetic characteristics of the test compound and knowledge of critical periods of susceptibility, can be used on a case-by-case basis to make more accurate extrapolations of test animal data to the human.

Animals↗
PubMed1991

Japanese encephalitis virus (JEV): potentiation of lethality in mice by microwave radiation.

The expression of Japanese Encephalitis Virus (JEV) lethality in mice requires entry of the virus into the central nervous system. This entry is presumably through the capillary endothelial cells (CEC), because entry between CECs is inhibited by bands of circumferential tight-junctions. A viremic stage occurs during the first 4 to 5 days after JEV administration in mice, and both microwave radiation (2.45-GHz, continuous wave, 10-min exposure) and hypercarbia were employed to increase CEC permeability to JEV. Exposure to microwaves at power densities of 10-50 mW/cm2 resulted in a dose-dependent increase in JEV-induced lethality. Mice did not become tolerant or sensitized to microwave potentiation of JEV-induced mortality because 4 daily exposures at 10 or 50 mW/cm2 (SARS, approximately 24-98 W/kg) did not alter the lethality pattern to subsequent microwave radiation of JEV-exposed animals. Similarly, hypercarbia (5, 10, and 20% CO2) was observed to produce a dose-dependent increase in JEV-induced lethality. Both microwave radiation and hypercarbia are thought to promote pinocytosis in CNS capillary endothelial cells. This may be one mechanism by which they enhance JEV-induced lethality in adult Swiss-Cox mice.

Animals↗
PubMed2005

Characterization of Amoeba proteus myosin VI immunoanalog.

Amoeba proteus, the highly motile free-living unicellular organism, has been widely used as a model to study cell motility. However, molecular mechanisms underlying its unique locomotion and intracellular actin-based-only trafficking remain poorly understood. A search for myosin motors responsible for vesicular transport in these giant cells resulted in detection of 130-kDa protein interacting with several polyclonal antibodies against different tail regions of human and chicken myosin VI. This protein was binding to actin in the ATP-dependent manner, and immunoprecipitated with anti-myosin VI antibodies. In order to characterize its possible functions in vivo, its cellular distribution and colocalization with actin filaments and dynamin II during migration and pinocytosis were examined. In migrating amoebae, myosin VI immunoanalog localized to vesicular structures, particularly within the perinuclear and sub-plasma membrane areas, and colocalized with dynamin II immunoanalog and actin filaments. The colocalization was even more evident in pinocytotic cells as proteins concentrated within pinocytotic pseudopodia. Moreover, dynamin II and myosin VI immunoanalogs cosedimented with actin filaments, and were found on the same isolated vesicles. Blocking endogenous myosin VI immunoanalog with anti-myosin VI antibodies inhibited the rate of pseudopodia protrusion (about 19% decrease) and uroidal retraction (about 28% decrease) but did not affect cell morphology and the manner of cell migration. Treatment with anti-human dynamin II antibodies led to changes in directionality of amebae migration and affected the rate of only uroidal translocation (about 30% inhibition). These results indicate that myosin VI immunoanalog is expressed in protist Amoeba proteus and may be involved in vesicle translocation and cell locomotion.

Actins↗
PubMed1987

Flow cytometric analyses of lectin binding to rat alveolar macrophages.

The binding characteristics of ten FITC-labeled plant lectins (Con-A, MPA, BPA, PNA, WGA, SBA, UEA-I, DBA, GS-I, GS-II) to lavaged rat alveolar macrophages were assessed by flow cytometry. The alveolar macrophages (AM) were incubated with varying concentrations of each lectin in a pinocytosis-inhibiting buffer. In addition to measuring lectin-associated green fluorescence, the electronic cell volumes and axial light loss characteristics of the AM were also measured flow cytometrically. These latter parameters were found to be good indicators of cell agglutination caused by some of the lectins, and, in conjunction with green fluorescence measurements, usefully serve to determine optimal or nonagglutinating lectin concentrations for flow cytometric studies. With the exception of UEA-I, all of the lectins examined bound to AM, although a wide range of binding was observed among the lectins. At subagglutinating concentrations, Con A, MPA, BPA, PNA, WGA, SBA, and GS-I bound to the AM with unimodal patterns. Histograms of lectin-associated fluorescence intensity obtained with DBA clearly presented a pattern consistent with a more complex, bimodal distribution of labeled AM, suggesting the presence of at least two subset populations. The low-intensity distribution of AM represented congruent to 70% of the cells, while the more strongly labeled subset represented congruent to 15% of the parent AM population. The remaining balance of the AM was identified as another subpopulation by the failure to detectably bind to the DBA. While GS-II bound to all of the AM, this lectin labeled about 5% of the cells much more intensely than the bulk of the population. Thus, two subset populations of AM could be resolved according to their differing avidities for the GS-II lectin.

Animals↗
PubMed1980

Macrophage handling of soluble immune complexes. Ingestion and digestion of surface-bound complexes at 4, 20 and 37 degrees C.

Radioassays have been developed to measure, as separate events, the ingestion and degradation of macrophage-bound guinea pig IgG anti-DNP (2,4-dinitrophenyl)-DNP-BSA (bovine serum albumin) complexes of defined size and subclass. Complex ingestion was observed to be temperature-dependent and was effectively blocked only by a combination of inhibitors of respiration and glycolysis indicating that the process is under the same metabolic control as fluid phase pinocytosis. On the other hand, the half-life of membrane-bound complexes at 37 degrees C (t1/2 = 5.6 +/- 1.7 min) was considerably shorter than the value expected from membrane turnover studies (t1/2 = 22.4 min) suggesting that complexes are selectively cleared from the cell surface. The rate of ingestion at 20 degrees C was independent of complex size and of the IgG subclass used in complex formation, but was affected by in vivo stimulation of the macrophages before assay. Complex digestion was shown to be highly temperature-dependent and, at 37 degrees C, proceeded at a rate (t1/2 = 15.5 h) which was 20-60-fold slower than the rate of ingestion indicating that the latter is unlikely to influence digestion kinetics. On the other hand, the selective action of 2-deoxyglucose in blocking digestion, but not ingestion, suggests that pinosome-lysosome fusion may play a part in determining the overall catabolic rate. A 2 to 3-fold difference in digestion rates was observed between the proteins employed as antibody (guinea pig IgG1 or IgG2) and as antigen (DNP-BSA). This finding suggests that the intrinsic susceptibility of ingested proteins to enzymatic hydrolysis may be the prime determinant of digestion rate. As with ingestion, no discrimination was observed in the degradation of complexes of different size or IgG antibody subclass. The observations in this and the preceding study (Eur. J. Immunol. 1980. 10:317) indicate that complex size is important in determining the level of uptake by phagocytes but not subsequent events associated with catabolism.

Animals↗
PubMed1992

Antigen presentation for T cell interleukin-2 secretion is a late acquisition of neonatal B cells.

The ability of B lymphocytes to process and present antigen to helper T cells is essential to initiate T cell-B cell interactions in humoral immune responses. Here we describe the developmental acquisition of the antigen-presenting function of B cells as measured by the ability of B cells to stimulate a T cell hybrid to interleukin (IL)-2 secretion. Neonatal splenic B cells are not adult-like in their ability to process and present the model protein antigen pigeon cytochrome (Pc), which enters the B cell through fluid-phase pinocytosis, until 21 to 28 days of life. The ability of neonatal B cells to process and present antigen which enters the cell bound to surface Ig is not adult-like until 28 days of age. When neonatal B cells acquire antigen-presenting cell (APC) function, surface IgM facilitates antigen processing. The delayed acquisition of APC function cannot be accounted for solely by a deficiency in major histocompatibility complex MHC class II, ICAM-1, or LFA-1 as neonatal B cells express adult levels of these molecules by 7-14 days after birth. Moreover, the ability of neonatal B cells to present a peptide fragment of Pc which does not require processing is adult like by day 14. Furthermore, neonatal B cells are capable of binding, internalizing and degrading radiolabeled antigen, suggesting a more subtle level of regulation. In contrast to neonatal B cells, immature B cells in the adult bone marrow and adult B cells undergoing antigen-driven differentiation to memory B cells, as defined by the loss of the J11D marker, are competent to process and present antigen resulting in T cell IL-2 secretion. Thus, developing B cell subpopulations in the adult and in the neonate can be distinguished. Only neonatal B cells are deficient in their ability to stimulate T cells to IL-2 production.

Animals↗
PubMed1995

CD40-CD40 ligand interactions stimulate B cell antigen processing.

The interactions between B cell CD40 and T cell CD40 ligand (CD40L) have been shown recently to play an important role in T cell-dependent activation of B cells. Here, we show that the ligation of CD40 stimulates the processing of antigen by B cells. The activation of an antigen-specific T cell hybrid by B cells co-cultured with insect cells expressing recombinant CD40L or with a CD40-specific monoclonal antibody requires less antigen and fewer B cells compared to control cells. The augmentation was observed both for processing initiated by antigen binding to and cross-linking the surface immunoglobulin, and processing of antigen taken up by fluid-phase pinocytosis. CD40 appears to affect a step in the intracellular processing of antigen, as CD40 has no effect on the presentation of an antigenic peptide which does not require processing. In addition, the CD40-induced augmentation of processing is not attributable to the effect of CD40 ligation on the cell surface expression of B7, LFA-1 or CD23. CD40 ligation does not affect the biosynthesis of the class II EK molecules, and although ligation of CD40 induces B cell proliferation, the augmentation of processing does not require proliferation. The ability of CD40 to stimulate B cell antigen processing has the potential to influence significantly the outcome of antigen-dependent T cell-B cell interactions.

Adjuvants, Immunologic↗
PubMedDate not supplied

Characterization of Chlamydia trachomatis l2-induced tyrosine-phosphorylated HeLa cell proteins by two-dimensional gel electrophoresis.

Chlamydia trachomatis is an obligate intracellular bacteria, inducing its own uptake in nonprofessional phagocytes either by phagocytosis or pinocytosis. We have previously shown that C. trachomatis L2 induces tyrosine phosphorylation of eukaryotic proteins upon their entry by phagocytosis. In this paper we characterize the tyrosine-phosphorylated proteins by two-dimensional gel electrophoresis. In immunoblotting with anti-phosphotyrosine antibodies of C. trachomatis L2-infected HeLa cells, but not with uninfected cells, two rows of spots were observed with a molecular mass of 69 and 71 kDa and pI from 5.0 to 5.2. In addition, a single spot of 100 kDa and pI 6.2 was observed.

Animals↗
PubMed1991

The role of capillarization in hepatic failure: studies in carbon tetrachloride-induced cirrhosis.

During the cirrhotic process, the hepatic microvascular phenotype is transformed from sinusoids (discontinuous capillaries) into continuous capillaries. This transformation has been termed capillarization. Many hepatic functions depend on the rapid, bidirectional exchange of macromolecules between plasma and hepatocytes. To determine whether capillarization contributes to hepatic failure in cirrhosis, we decided to study the plasma clearance (125I) and hepatocyte uptake (electron microscopy) of three tracers in normal and cirrhotic rats. The tracers chosen were a hemeundecapeptide with peroxidatic activity (fluid-phase pinocytosis), asialofetuin (receptor-mediated endocytosis of a medium size protein) and ferritin (receptor-mediated endocytosis of a large size protein). The results demonstrate a decreased hepatocyte uptake of hemeundecapeptide; a significant delay in plasma clearance of asialofetuin; and a minor delay in plasma clearance of ferritin, but a striking trapping of ferritin in the cirrhotic capillary basement membrane. The delayed plasma clearance in cirrhosis cannot be ascribed to a decreased number of surface receptors because, in isolated hepatocytes, the number of molecules bound per cell was equivalent in normal and cirrhotic livers. These findings support the concept of capillarization, with the formation of continuous diffusion and filtration barriers between plasma and hepatocytes, representing a significant hindrance to the bidirectional macromolecular exchange normally taking place between these two compartments. Furthermore, at least in the case of ferritin, the capillary basement membrane of cirrhotic livers seems to be the major filtration barrier. This hindrance to hepatocyte uptake, and presumably also to secretion, may be the cause (or at least a major determinant) of the hepatic failure characteristic of cirrhosis.

Animals↗
PubMed1976

Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia.

The K562 cell line derived from a CML patient in blast crisis was examined for properties of B and T lymphocytes and cell lines. K562 lacks the B markers of immunoglobulins, Epstein-Barr virus (EBV) genome and associated nuclear antigen, and receptors for EBV. A low proportion of cells from rosettes with sheep erythrocytes, the frequency of which is considerably increased after neuraminidase treatment. Unlike B lines but like T lines, K562 cells are lysed rapidly by C'/Fc receptor-positive human blood leukocytes and do not stimulate MLC reactions. On the other hand, K562 lacks T antigen, high radiosensitivity and sensitivity to growth inhibition by thymidine. The cells do not contain N-APase, an enzyme found in all lines derived from lymphoid cells and in lymphoproliferative diseases. By scanning electron microscopy, K562 cells were seen to be rounded and relatively smooth, with small numbers of short microvilli resembling undifferentiated leukemic cells. A few cells had narrow ridge-like profiles and small ruffles similar to granulocytic leukemic cells. K562 is strongly positive for immunoglobuln Fc receptors and pinocytosis, but does not phagocytose or mediate antibody-dependent phagocytosis or cytolysis. Among histochemical stains, K562 is positive for esterase, lipid, and acid phosphatase. There seems to be no doubt that K562 is not a B cell line. While it has some T cell properties, these are not exclusive. Some of its characteristics indicate that it is probably not lymphoid. Due to its low level of differentiation, its nature cannot be stated with certainty. On the basis of the possible presence of the cellular marker of chronic myeloid leukemia, the Ph chromosome, it may be regarded as belonging to the granulocytic series of cells.

Alkaline Phosphatase↗
PubMed1991

Ni3S2 uptake by lung cells and its interaction with plasma membranes.

The uptake and biological transformation of Ni3S2 was studied on guinea pig alveolar macrophages (GPAM) in primary culture. Two different pathways are observed: (i) phagocytosis of alpha Ni3S2 crystals and subsequent degradation to minute particles, which are recovered bound to the membranes of phagocytic vacuoles and to lysosomal membranes. These degradation products contain sulphur in very reduced quantities, as revealed by energy-dispersive spectrometry (EDS). (ii) Extracellular degradation to regular round particles (0.1-0.2 microns) and irregular minute particles (10-30 nm). Round particles may enter the cell by pinocytosis and are characterized by the loss of sulphur. Minute particles are bound preferentially to cell membranes, to cytoplasmic organelles, such as endoplasmic reticulum, mitochondria and peroxysomes, to liposomes and to the euchromatinic part of nuclei. EDS analyses in these particles revealed the substitution of sulphur by phosphorus. This observation suggests the formation of an Ni-P complex with the phosphate groups of membranous and liposomal phospholipids and of the euchromatinic part of DNA or RNA. Steady-state fluorescence polarization analysis were carried out on GPAM and, for comparative purposes, on human embryonic pulmonary epithelial cells (L132 cell line). In both cell types they revealed a significant increase of membrane fluidity, induced either by desaturation of aliphatic chains or directly by the cleavage of fatty acid chains.

Cell Membrane↗
PubMed1992

Human neutrophil response to short-term exposure to F-75 cobalt-based alloy.

The effect of biomaterials on the activation of human neutrophils was studied. Human neutrophils were incubated with F-75 cobalt-based alloy or polystyrene microspheres of a nonphagocytosable size with two times total neutrophil plane surface area. Scanning and transmission electron microscope (SEM, TEM), energy dispersive x-ray microanalysis (EDX), and graphite furnace atomic absorption spectroscopy (GFAAS) were used to analyze changes in cellular morphology and metal content. This report presents evidence that human PMNs display morphological changes related to foreign material challenge, including activation on F-75 bead surfaces, pinocytosis of corrosion products, formation of intracellular vacuoles, degranulation, etc. Moreover, when PMNs were present, the corrosion release rate of F-75 increased as much as three times over cell-free controls.

Adult↗
PubMed1982

Intracellular accumulation of a fluorescent derivative of paromomycin in human fibroblasts.

Human fetal lung fibroblasts grown in the presence of dansyl-paromomycin (DNS-Pm), a fluorescent derivative of the aminoglycoside antibiotic, paromomycin, probably accumulate DNS-Pm in the lysosomes. The intracellular concentration of DNS-Pm is proportional to the extracellular concentration and to the length of time cells are exposed to the compound. The accumulation of DNS-Pm by human fibroblasts continued to increase for several days, reaching a saturation after 7 days. The kinetic data are consistent with the establishment of a steady state in the cell between fluid-phase pinocytosis and exocytosis of DNS-Pm. About 80% of the intracellular DNS-Pm ws released in 24 hr when fresh medium without the analogue was added. The residual 20% remained within the cells, suggesting that it may be irreversibly bound to the lysosomes, endoplasmic reticulum, or ribosomes. The uptake of paromomycin by cells in culture may be a useful means to study error propagation during growth and lifespan of cells in vitro.

Chemical Phenomena↗