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S L Carlson

Publications and source records attributed to S L Carlson.

30 records · Page 2Linked to original sources
PubMed1994

Enhancement of beta-adrenergic-induced cAMP accumulation in activated T-cells.

Agonist stimulation of the beta-adrenergic receptor on T-cells results in the production of cAMP, which has been correlated with modulation of T-cell function. In previous studies, we have demonstrated that the mitogen PHA can synergistically enhance the accumulation of cAMP in T-cells in response to the agonist isoproterenol. In this report we have investigated the mechanisms by which dual stimulation of T-cells acts to synergistically enhance cAMP accumulation. The results demonstrate that increasing the levels of intracellular calcium with ionomycin or thapsigargin enhanced isoproterenol-induced cAMP accumulation in T-cells. In contrast, PHA enhanced isoproterenol-induced cAMP by a calcium-independent mechanism as evidenced by stimulation with isoproterenol plus PHA in calcium-free medium. Further studies revealed that PHA prevented both sequestration of the beta-adrenergic receptor and its dissociation from Gs protein in response to isoproterenol stimulation. In contrast, PHA did not prevent the functional uncoupling of the beta-adrenergic receptor from adenylyl cyclase, suggesting that additional mechanisms are likely involved. In summary, these studies demonstrate that dual receptor signalling of T-cells increases cAMP accumulation and offers a potential mechanism for catecholamine modulation of T-cell function.

Calcium↗
PubMed1990

Fluorescence histochemical techniques for catecholamines as tools in neurobiology.

Formaldehyde-induced and glyoxylic-acid-induced fluorescence histochemistry permits the tissue localization of catecholamines in the central nervous system (CNS) and peripheral nervous system (PNS), and in culture. Counterstains such as ethidium bromide provide excellent background identification of specific innervated regions in both the CNS and the periphery. Use of fluorescence histochemistry with immunocytochemistry can elucidate catecholamine-peptide relationships. Gelatin-ink perfusion used with fluorescence histochemistry permits the investigation of neuro-vascular relationships and documentation of vascular and parenchymal compartmentation of innervation. Combined use of fluorescence histochemistry and retrograde tracing methods demonstrates the specific cellular sources of innervation of target regions. Micropunch neurochemical analysis provides quantitative data for correlation with fluorescence histochemistry within a target region of innervation, and microspectrofluorometric analysis provides a semi-quantitative evaluation of the amount of fluorophore within a target region or within specific subcellular compartments such as the cell body or terminals.

Animals↗
PubMed1989

Neurotransmitter-lymphocyte interactions: dual receptor modulation of lymphocyte proliferation and cAMP production.

Stimulation of the beta-adrenergic receptor on lymphocytes can decrease the proliferative response of these cells to mitogens. We have found that simultaneous stimulation of T cells with the beta-adrenergic agonist isoproterenol and mitogens (phytohemagglutinin (PHA) and OKT3 monoclonal antibody) results in a 2- to 4-fold increase in cAMP production compared to cells exposed to isoproterenol alone. Mitogens alone have little effect on cAMP synthesis, but do activate the phosphatidylinositol (PI) cycle, suggesting that interactions may be occurring between the second messenger systems resulting in a cAMP synergy. Further experiments suggest that calcium may be involved in inducing the cAMP synergy observed in T cells. It is proposed that the synergy between beta-adrenergic and mitogenic stimulation of T cells for cAMP may be involved in the mechanism of catecholamine modulation of lymphocyte function.

Cyclic AMP↗
PubMed1987

Noradrenergic sympathetic innervation of the spleen: V. Acute drug-induced depletion of lymphocytes in the target fields of innervation results in redistribution of noradrenergic fibers but maintenance of compartmentation.

Sympathetic noradrenergic fibers follow the vasculature into the white pulp of the spleen and branch from the periarteriolar plexuses into T lymphocyte zones. These lymphocytes, reported to express adrenergic receptors, are contacted directly by norepinephrine (NE) terminals and are putative targets of the locally released NE. Although this splenic innervation has been studied extensively, the functional interdependence of the lymphocytes and the sympathetic innervation is not well understood. To assess the effect of acute lymphocyte loss on the splenic innervation, T and B lymphocytes were depleted through treatment with cyclophosphamide (CY) or hydrocortisone acetate (HC). Despite reductions in spleen weight and cellularity, the total NE content (pmol) per spleen did not change. However, the NE concentration increased in the treated spleens. Although the general compartmental organization of the noradrenergic fibers in the treated spleens was similar to that of controls, the NE fibers redistributed and increased in density around the smaller central arteries in lymphocyte depleted spleens. The accommodation of these NE fibers to the changing environment of the white pulp suggests that the innervation to the spleen remains chemically stable despite a large disruption to the normal splenic milieu, but is capable of plasticity in the face of a shrinking white pulp.

Animals↗
PubMed1987

Alterations of monoamines in specific central autonomic nuclei following immunization in mice.

At the peak of an immune response (Day 4 following immunization) in mice, norepinephrine (NE) was selectively decreased in the paraventricular nucleus (PVN) of the hypothalamus. At times before (Day 2) and after (Day 8) the peak immune response, no changes in NE were found in this nucleus. Decreases in NE were not seen in other hypothalamic sites or in the A1 cell group of the medulla, which sends noradrenergic projections to the hypothalamus, suggesting that the effect is selective and regional. Morphometric evaluation of varicosities revealed no alterations in density of catecholamine-containing varicosities in the PVN, further suggesting that the decrease in NE is a metabolic effect and not a loss or redistribution of fibers. NE also was decreased in the hippocampus on Day 2 at the rising phase of the immune response. In addition, alterations in serotonin levels were found in the brain during an immune response. Serotonin was decreased in the hippocampus on Day 2, was decreased in the PVN and supraoptic nucleus on Day 4, and was increased in the nucleus tractus solitarius (NTS) on Day 2. These results support the presence of a functional link from the activated immune system to central autonomic nuclei interconnecting the hypothalamus, the limbic system, and the autonomic nervous system. In view of the role of the PVN in corticotropin-releasing factor secretion and regulation of autonomic outflow, evidence from lesion studies for hippocampal involvement in immune regulation, and a key role for NTS in regulation of autonomic outflow, the present findings reinforce the potential importance of these brain regions in reciprocal communication between the nervous and immune systems.

Animals↗
PubMed1985

Cup cells: further structural characterization of the brush border and the suggestion that they may serve as an attachment site for an unidentified bacillus in guinea pig ileum.

We recognized a low incidence, spontaneously occurring colonization of guinea pig ilea by an unidentified strain of gram-negative bacteria. By thick section, bacteria were associated with 28% of cup cells but with only 0.4% of absorptive cells. Additionally, noncolonized guinea pig ileum was subsequently studied by a variety of morphologic techniques to further define the normal functional anatomy of cup cells. Cup cells have glycocalyces that are more extensive than those of absorptive cells. As judged by ruthenium red staining, cup cells are comparable to absorptive cells in the density of glycocalyceal anionic sites; thus cup cells would not be expected to bind negatively charged plasma membranes (like those of bacteria) simply on the basis of having diminished negative charge of the glycocalyx. Sequential studies of ileal loops exposed to cationized ferritin suggest cup cell microvilli are able to internalize small quantities of membrane-bound molecules but, like absorptive cells, transport these substances to lysosomelike compartments. Finally, we show that cup cells, unlike absorptive cells, readily display morphologically detectable cholesterol on their microvillus membranes, even though it is likely that cup cell microvillus membranes are highly stabilized by underlying cytoskeleton as are those of absorptive cells, which label poorly for morphologically detectable cholesterol. These studies further define cup cell structure and suggest that these cells may represent preferential sites for attachment of at least some strains of bacilli.

Animals↗
PubMed1985

Involvement of peripheral and central catecholamine systems in neural-immune interactions.

In this review, we have attempted to delineate the current state of knowledge of the relationships between the immune system and one chemically specific component of the nervous system, the noradrenergic system, both in the brain and the periphery. We have discussed recent work describing the presence of noradrenergic innervation in lymphoid tissues in the major lymphatic organs. Our findings demonstrate clearly that the regions in which lymphocytes (mainly T cells) reside, and through which they recirculate, receive direct sympathetic neural input. The immune system can, therefore, be considered 'hard-wired' to the brain. The evidence for receptors on cells of the immune system capable of receiving signals from the brain is discussed. The significance of this 'hard-wiring' to the function of the immune system is considered, both with regard to the effect of its disruption on immune responses, and to the direct and indirect effects of sympathetic neurotransmitter substances on lymphocytes and their behavior in vitro and in vivo. Finally, our detailed analysis of changes occurring in central noradrenergic pathways as a result of stimulation of the immune system leads to an emerging picture of feedback loops from the immune system to the brain. Such circuits employ endocrine, and probably autonomic, outflow to modulate and regulate immune responses.

Adrenergic Fibers↗
PubMed1985

Noradrenergic and peptidergic innervation of lymphoid tissue.

Sympathetic noradrenergic nerve fibers innervate both the vasculature and parenchymal fields of lymphocytes and associated cells in several lymphoid organs, including the thymus, spleen, lymph nodes, gut-associated lymphoid tissue (GALT), and bone marrow, in a variety of mammalian species. This innervation is both regional and specific, and generally is directed into zones of T lymphocytes and plasma cells rather than into nodular regions or B lymphocyte regions. In the thymus, noradrenergic fibers enter with nerve bundles and plexuses around blood vessels, travel into the cortex from subcapsular plexuses and with the vasculature, and branch into the parenchyma of the thymic cortex. The vasculature and parenchymal regions of both the outer and deep cortex are innervated by these fibers. In the spleen, noradrenergic fibers enter with the vasculature, travel along the trabeculae and along the branching vasculature, and are distributed mainly in the white pulp along the central artery and associated periarterial lymphatic sheath. Fibers branch from a dense plexus around the central artery and travel into the parenchyma, where they end among fields of lymphocytes and other cell types. In lymph nodes, noradrenergic fibers enter at the hilus, travel along the vasculature and in a subcapsular plexus, and branch into the parenchyma in paracortical and cortical regions, where they end among lymphocytes. In the GALT, represented in these studies by rabbit appendix, sacculus rotundus, and Peyer's patches, noradrenergic fibers enter at the serosal surface, travel longitudinally with the muscularis interna, turn radially into internodular plexuses, plunge directly through the thymus-dependent zones, and ramify profusely among lymphocytes, enterochromaffin cells, and plasma cells in the interdomal regions. In the bone marrow, noradrenergic fibers enter with blood vessels, distribute deeply into the marrow on those vessels, and branch sparsely into the substance of the marrow. Immunocytochemical observations revealed the presence of neuro-peptide-like immunoreactivity in the thymus and spleen. Vasoactive intestinal peptide (VIP)-like immunoreactivity is found in varicose profiles in the thymus within the cortex. In the spleen, immunoreactive profiles showing neuropeptide Y-like, Met-enkephalin-like, cholecystokinin-8 (CCK)-like, and neurotensin-like immunoreactivity are present along the central artery of the white pulp and its smaller branches, with only sparse fibers of most of these peptides entering the parenchyma. CCK-like profiles are present in abundance in the white pulp among parenchymal elements.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗
PubMed1984

Partitioning of paracellular conductance along the ileal crypt-villus axis: a hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationships.

Current models of intestinal transport suggest cells which absorb ions are located on the villus while secretory cells are located in the crypt and putatively have paracellular pathways which are highly conductive to Na+. One approach to assess possible variation in small intestinal paracellular conductance along the crypt-villus axis is to morphometrically analyze the structural aspects of crypt and villus tight junctions (TJs) which relate to paracellular resistance. Such detailed analysis of junctional structure in this heterogeneous epithelium would permit one to compare intestinal TJ structure-function relationships with those in a structurally simpler epithelium such as that of toad urinary bladder. This comparison would also be of considerable interest since previous similar comparisons have failed to consider in detail the geometric dissimilarity between these two epithelia. We applied light, electron microscopic, and freeze-fracture morphometric techniques to guinea pig ileal mucosa to quantitatively assess, for both crypts and villi, linear TJ density, relative surface contributions, and TJ strand counts. Mean linear TJ densities were 76.8 m/cm2 for crypt cells and 21.8 m/cm2 for villus absorptive cells. Mean TJ strand counts were 4.45 for undifferentiated crypt cell TJs and 6.03 for villus absorptive cell TJs. The villus constituted 87% and the crypt 13% of total surface. We utilized these data to predict paracellular conductance of crypts vs. villi based on equations derived from those of Claude (P. Claude, J. Membrane Biol. 39:219-232, 1978). Such analysis predicts that 73% of ileal paracellular conductance is attributable to the crypt. Furthermore, we obtained literature values for paracellular resistance in mammalian ileum and toad urinary bladder and for toad bladder TJ structure and linear density and constructed a relationship which would allow us to more accurately compare TJ structure-function correlates between these two epithelia. Such a comparison, which considers both surface amplification and TJ structure and distribution in these epithelia, shows that one would predict in vitro measured values for paracellular resistance should be approximately two orders of magnitude less in mammalian ileum than in toad urinary bladder. This predicted discrepancy (115-fold) correlates well with the observed difference (100-fold).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Sympathetic innervation of lymph nodes in mice.

Noradrenergic innervation of popliteal and mesenteric lymph nodes in mice was examined with fluorescence histochemistry. Dense varicose plexuses entered the nodes with the vasculature in the hilar region and continued with the vasculature into the medullary region. Fine, delicate varicosities and small vascular plexuses continued into the cortical and paracortical regions surrounding the germinal centers; some varicosities ended among lymphocytes. A subcapsular plexus contributed fibers into the cortical and paracortical regions. Chemical measurements revealed the presence of norepinephrine in lymph nodes that was depletable with 6-hydroxydopamine. Depletion of norepinephrine from lymph nodes with this agent resulted in a diminished primary immune response in draining lymph nodes following subcutaneous injection of an antigen in two mouse strains, but had no effect in two other strains. These findings suggest that noradrenergic fibers innervate both the vasculature and parenchymal regions of lymph nodes, and may participate in the modulation of immune responses in these organs.

Adrenergic Fibers↗