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At least 541 records · Page 30Linked to original sources
PubMed2000

Regulation of immunologic homeostasis in peripheral tissues by dendritic cells: the respiratory tract as a paradigm.

Dendritic cells are now recognized as the gatekeepers of the immune response, possessing a unique potential for acquisition of antigens at extremely low exposure levels and for efficient presentation of these in an immunogenic form to the naive T-cell system. Dendritic cell populations throughout the body exhibit a wide range of features in common that are associated with their primary functions, and these are considered in the initial section of this review. In addition, it is becoming evident that the properties and functions of these cells are refined by microenvironmental factors unique to their tissues of residence, a prime example being mucosal microenvironments such as those in respiratory tract tissues, and the latter represents the focus of the second section of this review.

Antibody Formation↗
PubMed1992

Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues.

Three inositol 1,4,5-trisphosphate receptor (IP3R) cDNAs, designated IP3R-II, -III, and -IV, were cloned from a mouse placenta cDNA library. All three display strong homology in membrane-spanning domains M7 and M8 to the originally cloned cerebellar IP3R-I, with divergences predominantly in cytoplasmic domains. Levels of mRNA for the three additional IP3Rs in general are substantially lower than for IP3R-I, though in the gastrointestinal tract the levels of IP3R-III may be comparable to IP3R-I. Cerebellar Purkinje cells express at least two and possibly three distinct IP3Rs, suggesting heterogeneity of IP3 action within a single cell.

Amino Acid Sequence↗
PubMed1995

The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues.

Ryanodine receptors (RyRs) are intracellular calcium release channels that participate in controlling cytosolic calcium levels. At variance with the probably ubiquitous inositol 1,4,5-trisphosphate-operated calcium channels (1,4,5-trisphosphate receptors), RyRs have been mainly regarded as the calcium release channels controlling skeletal and cardiac muscle contraction. Increasing evidence has recently suggested that RyRs may be more widely expressed, but this has never been extensively examined. Therefore, we cloned three cDNAs corresponding to murine RyR homologues to carry a comprehensive analysis of their expression in murine tissues. Here, we report that the three genes are expressed in almost all tissues analyzed, where tissue-specific patterns of expression were observed. In the uterus and vas deferens, expression of RyR3 was localized to the smooth muscle component of these organs. In the testis, expression of RyR1 and RyR3 was detected in germ cells. RyR mRNAs were also detected in in vitro-cultured cell lines. RyR1, RyR2, and RyR3 mRNA were detected in the cerebrum and in the cerebellum. In situ analysis revealed a cell type-specific pattern of expression in the different regions of the central nervous system. The differential expression of the three ryanodine receptor genes in the central nervous system was also confirmed using specific antibodies against the respective proteins. This widespread pattern of expression suggests that RyRs may participate in the regulation of intracellular calcium homeostasis in a range of cells wider than previously recognized.

Animals↗
PubMed2006

An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues.

Transfer of T cells to freshly irradiated allogeneic recipients leads to their rapid recruitment to nonlymphoid tissues, where they induce graft-versus-host disease (GVHD). In contrast, when donor T cells are transferred to established mixed chimeras (MCs), GVHD is not induced despite a robust graft-versus-host (GVH) reaction that eliminates normal and malignant host hematopoietic cells. We demonstrate here that donor GVH-reactive T cells transferred to MCs or freshly irradiated mice undergo similar expansion and activation, with similar up-regulation of homing molecules required for entry to nonlymphoid tissues. Using dynamic two-photon in vivo microscopy, we show that these activated T cells do not enter GVHD target tissues in established MCs, contrary to the dogma that activated T cells inevitably traffic to nonlymphoid tissues. Instead, we show that the presence of inflammation within a nonlymphoid tissue is a prerequisite for the trafficking of activated T cells to that site. Our studies help to explain the paradox whereby GVH-reactive T cells can mediate graft-versus-leukemia responses without inducing GVHD in established MCs.

Animals↗
PubMed2005

Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals.

The majority of maturing T lymphocytes that recognize self-antigens is eliminated in the thymus upon exposure to their target antigens. This physiological process of negative selection requires that tissue-specific antigens be expressed by thymic cells, a phenomenon that has been well studied in experimental animals. Here, we have examined the expression in human thymi of four retinal antigens, that are capable of inducing autoimmune ocular disease retinal S-antigen (S-Ag), recoverin, RPE65 and inter-photoreceptor retinoid-binding protein (IRBP)], as well as four melanocyte-specific antigens, two of which are used as targets for melanoma immunotherapy [gp100, melanoma antigen recognized by T cells 1, tyrosinase-related protein (TRP)-1 and TRP-2]. Using reverse transcription (RT)-PCR, we found that all thymic samples from the 18 donors expressed mRNA transcripts of most or all the eight tested tissue antigens. Yet, the expression of the transcripts varied remarkably among the individual thymic samples. In addition, S-Ag, RPE65 and IRBP were detected by immunostaining in rare cells in sections of human thymi by antibodies against these proteins. Quantitative real-time RT-PCR analysis revealed that the retinal antigen transcripts in the human thymus are present at trace levels, that are lower by approximately five orders of magnitude than those in the retina. Our observations thus support the notions that thymic expression is a common feature for all tissue-specific antigens and that the levels of expression play a role in determining the susceptibility to autoimmunity against these molecules.

Antigens, Neoplasm↗
PubMed1992

Regional hemodynamic effects and clearance of endothelin-1 in humans: renal and peripheral tissues may contribute to the overall disposal of the peptide.

We investigated the regional balance of endothelin-1 across the renal and leg vascular bed as well as the hemodynamic effects of exogenously administered endothelin-1 in six healthy men. Net regional endothelin-1 balance was calculated from the respective arteriovenous differences in plasma concentrations and the corresponding plasma flow, the latter being determined by para-aminohippurate or indocyanine-green dye using appropriate catheter techniques. During constant intravenous (i.v.) infusion of endothelin-1 (0.4 pmol/kg/min), a slight increase in diastolic blood pressure (p less than 0.05) and a decrease in heart rate (p less than 0.01) were observed. In contrast, no significant changes in leg hemodynamics were noted. Renal plasma flow decreased by approximately 30%, and renal vascular resistance increased by 50% as compared with the control (placebo) period (p less than 0.01). Renin plasma concentrations did not change substantially during endothelin-1 infusion. During the control (placebo) period, arterial endothelin-1 plasma concentrations averaged 2.1 +/- 1.0 pM. An equilibrated peptide balance across the leg and a slight renal uptake of endothelin-1 was observed. After endothelin-1 infusion, arterial plasma concentrations of the peptide increased to 4.9 +/- 1.3 pM (p less than 0.01), and a net overall renal and limb uptake of endothelin-1 accounted for approximately 9 and 6% of the infused endothelin-1 amount, respectively. Results showed that at systemic endothelin-1 plasma concentrations, comparable to those which occur in a variety of pathologic conditions such as hypertension or cardiogenic shock, besides pulmonary clearance, renal and limb uptake of the peptide may also contribute to the short half-life (t1/2) of endothelin-1 in humans.

Adult↗
PubMed1981

Dopamine and noradrenaline levels in peripheral tissues of several mammalian species.

Tissue levels of dopamine (DA) and noradrenaline (NA) have been compared in atrium, spleen, mesenteric artery, vas deferens and renal cortex of sexually mature rats, guinea-pigs, ferrets, rabbits and cats. The results suggest the presence of dopaminergic autonomic axons in the cat renal cortex, as has been previously reported for the dog. Such nerves are probably sparse or absent in the kidneys of the other species examined.

Animals↗
PubMed2004

Nicastrin expression in mouse peripheral tissues is not co-ordinated with presenilin and is high in muscle.

Nicastrin was the first binding partner of presenilin (PS) shown to be a critical component of the presenilin/gamma-secretase complex essential in development and differentiation, and in generation of Alzheimer's disease Abeta amyloid peptide. To investigate the function of this glycoprotein, we compared nicastrin and presenilin protein expression in various mouse tissues. Western blot analysis of PS1, PS2 and nicastrin indicates their expression levels are not coordinated. In adult mouse, nicastrin is highly expressed in muscle membranes, whereas presenilin levels are very low. By Blue Native electrophoresis, a PS1 complex of 400 kDa was detected in lung, brain, thymus and heart; nicastrin was also detected as a 400-kDa complex in brain but in muscle it was detected with a complex mobility of 240 and 290 kDa, suggesting association with alternate protein complexes. Immunocytochemistry confirms strong intracellular expression of nicastrin in skeletal muscle and blood vessel smooth muscle. These findings suggest a function for nicastrin in muscle other than participation in the gamma-secretase complex.

Amyloid Precursor Protein Secretases↗
PubMed1990

Neomycin and omega-conotoxin GVIA interact at a common neuronal site in peripheral tissues.

1. The present study examined the interaction of omega-conotoxin GVIA (omega-CT) and aminoglycoside antibiotics on electrically evoked, nerve-mediated contractile responses in the rat vas deferens, guinea-pig ileum and guinea-pig left atria. 2. omega-CT caused a time- and concentration-dependent inhibition of the electrically evoked twitch responses of the rat vas deferens and guinea-pig ileum. Aminoglycoside antibiotics inhibited the twitch responses of these preparations with a rank order of potency: neomycin greater than gentamycin greater than kanamycin. omega-CT had no effect on the postjunctional contractile responses of either noradrenaline (vas deferens) or carbachol (ileum). However, at high concentrations neomycin and gentamycin caused significant postjunctional inhibition. The results suggest that omega-CT and aminoglycosides cause prejunctional inhibition in these preparations, with the aminoglycoside antibiotics exhibiting postjunctional inhibitory effects as well at high concentrations. 3. omega-CT caused a concentration- and frequency-dependent inhibition of the neuronally mediated field stimulation enhancement of electrically paced guinea-pig left atria. omega-CT had no effect on either the electrically paced contractile response that was elicited by direct muscle stimulation or the enhancement of the paced response caused by beta-adrenoceptor agonist stimulation. Neomycin caused a concentration-dependent inhibition of the electrically paced contractile response and inhibited the field stimulation response only at concentrations which caused pronounced inhibition of the paced response. Neomycin also caused insurmountable inhibition of responses elicited by beta-adrenoceptor agonist stimulation. Thus, omega-CT caused an exclusive prejunctional inhibition in guinea-pig left atria, whereas the substantial postjunctional effects of neomycin made it difficult to discern any prejunctional activity of neomycin in these experiments. 4. In the vas deferens, ileum and atria the inhibitory effects of omega-CT were long-lasting, whereas the effects of neomycin could be reversed upon wash-out. The disparate kinetics of omega-CT and neomycin allowed for the design of receptor protection studies to determine whether neomycin acts at a prejunctional site in common with omega-CT. The pre-equilibration of a competitive antagonist (neomycin) should prevent the irreversible antagonist (omega-CT) from gaining access to receptors. Pre-exposure of tissues with neomycin prevented the irreversible inhibition of omega-CT. These receptor protection studies suggest that omega-CT and neomycin interact at common neuronal sites in the rat vas deferens, guinea-pig ileum and guinea-pig atria. Neomycin, however, exhibits activity at postjunctional sites as well.

Animals↗