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Biomedical subjects

E Weihe

Publications and source records attributed to E Weihe.

At least 91 records · Page 5Linked to original sources
PubMed1992

Changes in peptidergic innervation in chronic pancreatitis.

We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.

Adult↗
PubMed1991

Tachykinin-, calcitonin gene-related peptide-, and protein gene product 9.5-immunoreactive nerve fibers in alveolar walls of mammals.

The presence and distribution of the presumed pan-neural marker protein gene product 9.5 (PGP)- and peptide-immunoreactive (ir) nerve fibers in alveolar walls of various species was investigated by light microscopic single and double staining immunohistochemistry. PGP-, tachykinin (TK)-, and calcitonin gene-related peptide (CRGP)-ir fibers were sparsely distributed in a similar pattern in alveolar walls of all species investigated. No vasoactive intestinal peptide-, peptide histidine isoleucine-, galanin-, and opioid-ir nerve fibers could be detected. PGP-ir fibers outnumbered those staining for TKs and CGRP. There was partial coexistence of PGP and TK as well as of TK and CRGP. PGP-, TK-, and CGRP-ir fibers were in close spatial relationships to the cells building up the alveolar walls and to alveolar capillaries. The function of PGP is unknown. TK- and CGRP-ir nerves in alveolar walls may be sensory and function as chemo-, stretch-, and/or immuno-receptors. TKs and CGRP released from alveolar fibers may influence the alveolar epithelium and the various non-epithelial alveolar cells, including immune cells. The alveolar TK and CGRP innervation may be of unrecognized importance in physiological and pathophysiological regulation of lung functions.

Animals↗
PubMed1991

Dual presence of chromogranin A-like immunoreactivity in a population of endocrine-like cells and in nerve fibers in the human anal canal.

Light microscopic immunohistochemistry was used to investigate the presence and distribution of chromogranin A-like immunoreactivity in the human anal canal. In the anal transitional zone (ATZ), anal duct and anal gland epithelium, a varied number of mostly elongated cells strongly stained for CGA, using an antibody directed to a highly species-conserved region of the CGA molecule or the monoclonal antibody LK2H10. The density of CGA-immunoreactive (ir) cells strikingly increased from the ATZ epithelium towards the anal gland epithelium. CGA-ir cells possessed single processes running perpendicularly to reach the epithelial surface and exhibited basal ramifications that extended parallel to the basal lamina. The number of CGA-ir cells in anal glands exceeded CGA-ir cells in the crypt-bearing colorectal-type mucosa. The abundant population of CGA-ir cells in the anal canal most likely represents a population of specialized endocrine or paracrine cells. CGA-like immunoreactivity was also present in anocutaneous Merkel cells. A sparse number of vascular and non-vascular CGA-ir varicose nerve fibers was present throughout the layers and rostrocaudal divisions of the anal canal and in the perianal skin. Proposed functions of CGA in neuroendocrine cells and nerves of the anal canal include calcium binding and regulation, secretory granule matrix formation, and generation of bioactive peptides.

Amino Acid Sequence↗
PubMed1991

Light microscopic immunoenzyme and electron microscopic immunogold cytochemistry reveal tachykinin immunoreactivity in Merkel cells of pig skin.

Light microscopic (LM) immunoenzyme and electron microscopic (EM) immunogold cytochemistry were used to demonstrate the presence and subcellular distribution of tachykinin (substance P)-like immunoreactivity in Merkel cells of pig skin. Merkel cells of sinus hair follicles were strongly immunoreactive for tachykinins. In contrast, tachykinin-like immunoreactivity was absent from or very weak in epidermal Merkel cells while subepidermal and some intraepidermal nerve fibres were clearly immunopositive for tachykinins. Postembedding immunogold cytochemistry on the EM level revealed that tachykinin-like immunoreactivity was confined to the secretory granules in Merkel cells. Tachykinin immunoreactivity was clearly absent from the axon of the Merkel cell-axon complex. The selective presence of tachykinin immunoreactivity in secretory granules strongly suggests that tachykinins are synthesized in cutaneous Merkel cells, at least of pig. This is a further indication for the concept that the Merkel cell is a member of the diffuse neuroendocrine system. However, the functional role of tachykinins like substance P and neurokinin A and of other peptides present in Merkel cells remains enigmatic.

Animals↗
PubMed1991

The neuroimmune connection in human tonsils.

The present light microscopic immunohistochemical study evaluates the distribution of peptidergic nerve fibers in human tonsil and describes their spatial relationship with specific cells of the immune system. Further, using a panneural marker protein gene product (PGP) 9.5, a qualitative evaluation of the density of specific peptidergic innervation of the human tonsil was performed. Nerve fibers staining for tachykinins, calcitonin gene-related peptide, neuropeptide Y, or vasoactive intestinal polypeptide/peptide histidine isoleucine showed characteristic distribution patterns, but constituted only a minor subfraction of the PGP 9.5-stained fiber population. Both peptide- and PGP 9.5-immunopositive fibers predominantly supplied the vasculature; nonvascular areas were less densely innervated. Double staining for surface antigens thought to be associated with subsets of lymphoid cells, i.e., T-cells, B-cells, granulocytes, and macrophages, and for peptides or PGP 9.5 revealed close proximity of characteristic subpopulations of neurochemically defined nerve fibers and the various immune cells. The presence of peptidergic nerve fibers among T-cells was more prevalent than peptidergic nerve fibers adjacent to macrophages. Few positively stained nerve fibers resided in B-cell compartments. Neuro-B-cell interrelations were extremely infrequent. Neuroimmune connections were restricted to paravascular, subepithelial, and interfollicular regions, while germinal centers were devoid of nerve supply. The results are compatible with the view that peptides, being present in small-diameter nerve fibers, could exert an indirect immunoregulatory role by influencing vascular tone and/or permeability. In quantitative terms, a direct neuroimmunomodulatory action of endogenous neurally derived peptides appears to be of minor importance, because nonvascular neuroimmune circuits were found infrequently and were regionally restricted. However, we cannot be sure that all fibers were stained. The functional state of the peptidergic and nonpeptidergic innervation of the human palatine tonsil may be of physiological and pathophysiological significance within the psycho-neuro-immuno-endocrine network. The peptide-coded neuroimmune link may play a role in tonsillar pain.

Biomarkers↗
PubMed1991

Interrelation of peptidergic innervation with mast cells and ED1-positive cells in rat thymus.

The peptidergic innervation of rat thymus has been investigated by immunohistochemical methods, focusing on the spatial interrelationship of peptidergic nerve fibers with mast cells and macrophages in the rat. An antiserum directed against the protein gene product 9.5 (PGP 9.5) regarded as a pan-neuronal marker revealed a rich innervation, especially in the subcapsular cortex, in interlobular septa, and of the vasculature in the cortex and the corticomedullary boundary. A minor proportion of PGP 9.5-immunoreactive (ir) fibers supplied the thymic parenchyma. The main component of peptidergic innervation consisted of fibers costaining for tachykinins (TKs) and calcitonin gene-related peptide (CGRP), but considerable amounts of neuropeptide Y (NPY)/tyrosine hydroxylase (TH)-positive fibers and vasoactive intestinal polypeptide/peptide histidine isoleucine-positive fibers also were present. There were sparse Leu-enkephalin and galanin immunoreactivities in thymic nerve fibers, while neurotensin was absent from nerve fibers. Close associations of TK/CGRP-ir and NPY-ir fibers with mast cells were frequently detected in the connective tissue areas of the thymus, often adjacent to the vasculature. TK/CGRP-ir fibers and some rare NPY-ir fibers were found adjacent to EDl-positive macrophages and less frequently to mast cells. TK/CGRP-ir and NPY-ir fibers were mainly detected in relation to the vasculature of the cortex and the corticomedullary boundary, but also were found in capsular and subcapsular regions of the thymic cortex. The possible importance of the close spatial relationship between the various peptide-containing nerve fibers and mast cells and ED1-positive macrophages in neuroimmune integration is discussed.

Animals↗
PubMed1991

The neuroimmune link in the bronchus-associated lymphoid tissue (BALT) of cat and rat: peptides and neural markers.

This light microscopic immunohistochemical study investigates the distribution and target interrelations of nerve fibers in bronchus-associated lymphoid tissues (BALT) of rat and cat by using antisera against (1) the polyneuronal marker protein gene product 9.5 (PGP 9.5), (2) selected opioid and nonopioid peptides, and (3) the marker enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). In both species, a similar distribution pattern of PGP, peptide, and catecholamine enzyme immunoreactive was observed. Anti-PGP 9.5 stained all nerve fibers (except some smaller, calcitonin gene-related peptide-immunoreactive (CGRP-ir) fibers presumably of the C-type) throughout the different compartments of BALT, e.g., under the epithelium, in the smooth muscle layer, along the vasculature, and between immune cells of BALT parenchyma. The distribution of fibers staining for peptides (substance P (SP), (CGRP), neuropeptide Y (NPY). Leu-enkephalin, Met-enkephalin-Arg-Gly-Leu) and/or the catecholamine enzymes was also not compartment-specific. However, the density of the different peptidergic fibers and those staining for the marker enzymes exhibited region- and target-specific variations, e.g., fibers, cocontaining substance P and CGRP were more ubiquitous in nonvascular regions than codistributed NPY-, TH-, and DBH-ir fibers, which clearly prevailed in perivascular plexus. Regularly, nerve fibers staining for any of the peptides and markers investigated formed close contacts with mast cells, cells of the macrophage/monocyte cell line (identified as ED1 + cells), and/or other lymphoid cells, although with different frequencies. We assume that the SP/CGRP innervation is mainly of primary sensory origin, while the NPY innervation is chiefly derived from postganglionic noradrenergic sympathetic neurons. The VIP/PHI component is most likely postganglionic cholinergic while the opioid component, apparently derived from the Proenkephalin precursor, could be of differential origin. We propose that the neuroimmune connections in BALT play a significant role in the regulation and/or modulation of physiological/pathophysiological mechanisms of the lung. BALT may also be an integral part of the psycho-neuro-immune axis.

Amino Acid Sequence↗
PubMed1991

The neuro-B cell link of peptidergic innervation in the Bursa Fabricii.

The Bursa Fabricii, restricted to birds, specifically provides the microenvironment for B-cell maturation. The presence of nerve fibers containing immunopotent neuropeptides in immune organs opens interesting perspectives on the understanding of neuroimmune communication. As an organ for the development of only B-lymphocytes is not known in mammals, the contribution of a peptidergic innervation to the microenvironment of B-cells is not known. Therefore, we studied the peptidergic innervation of the Bursa Fabricii as an organ of B-cell maturation. Four different neuropeptides were found in nerve fibers of the Bursa Fabricii: tachykinins (TK), vasoactive intestinal peptide (VIP), galanin (GAL), and calcitonin gene-related peptide (CGRP). All these neuropeptides were distributed throughout the different bursal compartments, with the exception of the medulla of the bursal follicles, where the early stages of lymphocyte maturation are found. Double immunofluorescent studies revealed three different fiber populations: One containing coexisting VIP and GAL, the second TK and CGRP, and the last TK and no CGRP. Some of the TK-ir fibers may contain coexisting VIP. As demonstrated by double labeling for neuropeptides and lymphocytes, these heterologous fiber populations were found adjacent to B-cells in the follicle cortex. In addition, VIP-ir fibers were seen in association with macrophages. The origins of the fiber populations and the possible functional implications of our findings are discussed.

Animals↗
PubMed1991

Molecular anatomy of the neuro-immune connection.

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.

Animals↗
PubMed1991

Peptidergic innervation of the Bursa Fabricii: interrelation with T-lymphocyte subsets.

In birds, B-lymphocytes mature in a special immune organ, the Bursa Fabricii. This organ thus offers unique possibilities for the study of the microenvironment of B-lymphocyte differentiation. We previously reported tachykinin-, vasoactive intestinal peptide-, calcitonin gene-related peptide- and galanin-immunoreactive (ir) fibres in the chicken bursa. As judged from light microscopic studies, each of the peptides was found in fibres contacting B-lymphocytes. Vasoactive intestinal peptide-ir fibres contacted macrophages. Now, we demonstrate neuropeptide Y, indicating the sympathetic nervous system, in fibres associated with arteries, not entering the follicles. CD4- and CD8-positive T-lymphocytes were dispersed in bursal follicles and the connective tissue, most densely in subepithelial regions. We could not find close apposition of fibres with either T-cell subset. We conclude that the potential neuro-immune axis in the Bursa Fabricii may represent a neuro-B-cell-link with only indirect participation of T-lymphocytes. The sympathetic input may influence the bursal microenvironment primarily by regulating the blood supply.

Animals↗
PubMed1990

Differential occurrence and distribution of galanin in adrenal nerve fibres and medullary cells in rodent and avian species.

The presence and distribution of galanin (GAL) in adrenal glands of rodent and avian species was investigated by light microscopic immunohistochemistry. GAL immunoreactivity was found in all medullary cells of guinea pig, duck and chicken adrenals. In contrast, only a subpopulation of medullary cells stained for GAL in Phodopus (Djungarian hamster) while the neuropeptide was completely missing in chromaffin cells of rat and pigeon. In rat, guinea pig and pigeon, GAL-immunoreactive nerve fibres were frequent in subcapsular regions and sparse in deeper cortical layers and in the chromaffin tissue. In contrast, only very few GAL fibres were found in Phodopus and no GAL fibres were observed in the adrenal glands of duck. In the chicken adrenal gland, fibres containing GAL were numerous throughout the organ and occurred in close vicinity to both steroidogenic as well as catecholaminogenic cells. The striking differences in the presence of GAL-positive cells and fibres are more pronounced between species within the rodent or avian group, respectively, than between the different vertebrate orders. The hitherto unknown and surprising variability of GAL expression and distribution in adrenal glands of various species suggests species-dependent functional (autocrine, paracrine and/or endocrine) roles of GAL in the neuroadrenal axis.

Adrenal Glands↗
PubMed1990

Distribution of Met-enkephalyl-Arg-Gly-Leu in rat larynx: partial coexistence with vasoactive intestinal polypeptide, peptide histidine isoleucine and neuropeptide Y.

Using light microscopic (LM) enzyme-immunohistochemistry on deparaffinized adjacent sections Met-enkephalyl-Arg-Gly-Leu (ME-RGL) immunoreactivity was found to partially coexist with immunoreactive neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in intrinsic laryngeal neurons of the rat. Further ME-RGL-immunoreactive (ir) fibres were found around glands in the subepithelium, in connective tissue of striated muscle and in the perichondrium, as well as around arterial and venous blood vessels. They frequently contacted mast cells and macrophages. The presence of ME-RGL indicates pro-enkephalin-related origin of this novel laryngeal opioid system. From the specific target relations and close interrelations of fibres staining for opioids with those staining for the other peptides--which are known to be more or less characteristic of the sympathetic (NPY), parasympathetic (VIP, PHI) and sensory (calcitonin gene-related peptide; CGRP) subdivisions of the peripheral nervous system--we deduce that opioid/non-opioid interactions might co-control various laryngeal functions, e.g. glandular secretion, blood flow, immune and inflammatory responses and/or might be of relevance in trophic mechanisms.

Animals↗
PubMed1990

Capsaicin desensitization in vivo is inhibited by ruthenium red.

The effect of systemic administration of Ruthenium Red on the excitatory and desensitizing effect of capsaicin was investigated in rats. Ruthenium Red was injected s.c. 30 min before capsaicin was administered. The excitatory effect of capsaicin on corneal, perivascular and visceral afferents was not influenced by treatment with Ruthenium Red. However, determination of the neuropeptide content and evoked neuropeptide release in peripheral organs and dorsal spinal cord 48 h after treatment showed that Ruthenium Red attenuated the 'desensitizing' effect of capsaicin at peripheral, but not at central, endings of primary afferents. On the other hand, a capsaicin-elicited autonomic reflex mediated by visceral afferents was still obtained in 9 of 14 rats that had received Ruthenium Red and capsaicin. The results indicate that a single dose of Ruthenium Red, which does not reduce the acute excitatory effect of capsaicin, reduces the desensitizing effect of capsaicin on peripheral endings of primary afferents in vivo. This long-lasting protective effect of Ruthenium Red suggests that it is possible to pharmacologically differentiate between the acute and chronic effects of capsaicin.

Animals↗
PubMed1990

Electron microscopic immunogold cytochemistry reveals chromogranin A confined to secretory granules of porcine Merkel cells.

By ultrastructural immunohistochemistry using the immunogold technique, immunoreactive (ir) Chromogranin A (CGA) was found to be confined to the secretory vesicles of porcine Merkel cells. CGA was present predominantly in the periphery of the electron-dense core and on the clear halo. These findings indicate that CGA is a regular constituent of Merkel cell secretory granules but probably not exclusively responsible for their electron opacity.

Animals↗
PubMed1990

CGRP-like immunoreactivity in sensory nerve endings of the Golgi tendon organ. A light- and electron-microscopic study in the grey short-tailed opossum (Monodelphis domestica).

Using light- and electron-microscopic immunohistochemistry, it was shown that primary sensory nerve endings in Golgi tendon organs of the grey short-tailed opossum (Monodelphis domestica) contain immunoreactivities to a polyclonal antibody directed against calcitonin gene-related peptide (CGRP). Myelinated afferent axons (6-9 microns in diameter) of the Golgi tendon organs stained moderately for CGRP. Sensory nerve endings within the sensory compartment of the Golgi tendon organs displayed electron-dense accumulations corresponding to dark-brown staining in adjacent semithin sections. On the outer surface of tendon organs C fibre bundles were observed showing CGRP-like immunoreactivity.

Animals↗
PubMed1989

Tachykinins, calcitonin gene-related peptide and neuropeptide Y in nerves of the mammalian thymus: interactions with mast cells in autonomic and sensory neuroimmunomodulation?

By the use of light microscopic (LM) immunohistochemistry the distribution of tachykinin (TK)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity in nerves supplying the mammalian (rat, mouse, guinea-pig, cat) thymus gland has been determined. There were no interspecies variations. Fibres staining for TK and CGRP completely overlapped indicating coexistence. They were present in the capsule, in interlobular septa and in the corticomedullary boundary and occurred in perivascular and paravascular plexus supplying arteries, veins and the microvasculature. Some TK/CGRP-immunoreactive (ir) fibres travelled between lymphoid cells and close contacts with mast cells were frequent. NPY-ir fibres were different from those staining for TK/CGRP and predominated in the perivascular plexus of arterial blood vessels. Only very rarely they coursed in the lymphoid parenchyma. Intimate contacts of NPY-ir fibres with mast cells were less frequent than those of TK/CGRP-ir fibres. We conclude that the NPY innervation is mainly sympathetic noradrenergic while thymic nerves coding for TK and CGRP are most likely of sensory origin. These pathways may play a differential neuroimmunomodulatory role in the thymus, possibly via interaction with mast cells.

Adrenergic Fibers↗
PubMed1989

Pancreastatin-like immunoreactivity in epidermal Merkel cells of pig and man.

By use of light microscopic immunohistochemistry it was shown that Merkel cells of pig and man stained for pancreastatin. In pig, evaluation of paired consecutive sections revealed a coexistence of pancreastatin and chromogranin A (CGA) in individual Merkel cells from all localisations. However, in man pancreastatin expression was variable and depended from the localization and the developmental stage. The present findings suggest that pancreastatin is not specific for the pancreas and the intestine. However, it remains to be elucidated whether pancreastatin is a widely distributed in peptide-containing neuroendocrine granules of cells of the diffuse neuroendocrine system (DNES) as has been established for CGA.

Adult↗