Close apposition of dynorphin-positive nerve fibres to lymphocytes in the liver suggests opioidergic neuroimmunomodulation.

TY - JOUR

T1 - Close apposition of dynorphin-positive nerve fibres to lymphocytes in the liver suggests opioidergic neuroimmunomodulation.

AU - Kaiser, Matthias J T

AU - Tiegs, Gisa

AU - Neuhuber, Winfried L

PY - 2003

Y1 - 2003

N2 - The liver is innervated by sympathetic efferent, spinal afferent, vagal afferent and probably also vagal efferent fibres. To assess potential functional roles of the various neuronal subsets, data on transmitter systems are of crucial importance. This study was aimed at elucidating a possible opioidergic system in the mouse and rat liver. In particular relationships of opioidergic neurons to immune cells were emphasised. Material from perfusion-fixed mice ( n=29) of different strains (BALB/c, NMRI, C57Bl6, SV 129 inbred) and Wistar rats ( n=7) was cryosectioned at 12-14 microm and incubated for single or double immunofluorescence. Antibodies directed against dynorphin A, met-enkephalin, endomorphin 1 and 2, mu, kappa- and delta-opioid receptors (MOR, KOR, DOR), tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), CD4, CD8 and macrophages were used. Binding sites were detected using Cy3-, FITC-, DTAF-, Cy2-, Alexa 555- and Texas red-tagged secondary antibodies. Specimens were analysed using confocal laser scanning microscopy (CLSM). Numerous nerve fibres staining for dynorphin were found in periportal areas of both mouse and rat livers. Neither met-enkephalin nor endomorphin could be detected in axons. No immunopositive neuronal cell bodies or other cellular elements were seen. All dynorphin positive fibres costained for TH while not every TH-positive fibre costained for dynorphin. Thus, most if not all dynorphin-positive nerve fibres may be of sympathetic origin. KOR immunostaining could be localised to round mononuclear cells which often costained for CD4, less frequently for CD8 and rarely for the pan-macrophage marker BM8. Altogether, about 45% of KOR-positive cells were identified as T-lymphocytes. In some instances, close appositions of dynorphin-positive axons to KOR-positive cells were revealed by CLSM. No KOR immunoreactivity was detected in nerve fibres. Hence, sympathetic neurons innervating the liver may interfere with inflammatory processes, in addition to their well-established beta(2)-adrenergic effect, via an opioidergic action on immune cells.

AB - The liver is innervated by sympathetic efferent, spinal afferent, vagal afferent and probably also vagal efferent fibres. To assess potential functional roles of the various neuronal subsets, data on transmitter systems are of crucial importance. This study was aimed at elucidating a possible opioidergic system in the mouse and rat liver. In particular relationships of opioidergic neurons to immune cells were emphasised. Material from perfusion-fixed mice ( n=29) of different strains (BALB/c, NMRI, C57Bl6, SV 129 inbred) and Wistar rats ( n=7) was cryosectioned at 12-14 microm and incubated for single or double immunofluorescence. Antibodies directed against dynorphin A, met-enkephalin, endomorphin 1 and 2, mu, kappa- and delta-opioid receptors (MOR, KOR, DOR), tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), CD4, CD8 and macrophages were used. Binding sites were detected using Cy3-, FITC-, DTAF-, Cy2-, Alexa 555- and Texas red-tagged secondary antibodies. Specimens were analysed using confocal laser scanning microscopy (CLSM). Numerous nerve fibres staining for dynorphin were found in periportal areas of both mouse and rat livers. Neither met-enkephalin nor endomorphin could be detected in axons. No immunopositive neuronal cell bodies or other cellular elements were seen. All dynorphin positive fibres costained for TH while not every TH-positive fibre costained for dynorphin. Thus, most if not all dynorphin-positive nerve fibres may be of sympathetic origin. KOR immunostaining could be localised to round mononuclear cells which often costained for CD4, less frequently for CD8 and rarely for the pan-macrophage marker BM8. Altogether, about 45% of KOR-positive cells were identified as T-lymphocytes. In some instances, close appositions of dynorphin-positive axons to KOR-positive cells were revealed by CLSM. No KOR immunoreactivity was detected in nerve fibres. Hence, sympathetic neurons innervating the liver may interfere with inflammatory processes, in addition to their well-established beta(2)-adrenergic effect, via an opioidergic action on immune cells.

KW - Animals

KW - Male

KW - Female

KW - Mice

KW - Mice, Inbred BALB C

KW - Rats

KW - Rats, Wistar

KW - Antigens, CD4/chemistry/immunology

KW - Antigens, CD8/chemistry/immunology

KW - Dopamine beta-Hydroxylase/biosynthesis

KW - Dynorphins/biosynthesis

KW - Endorphins/biosynthesis

KW - Enkephalin, Methionine/biosynthesis

KW - Liver/cytology/innervation/metabolism

KW - Nerve Fibers/chemistry

KW - Neuroimmunomodulation

KW - Receptors, Opioid/biosynthesis

KW - Sympathetic Nervous System/cytology/metabolism

KW - T-Lymphocytes/cytology/immunology/metabolism

KW - Tyrosine 3-Monooxygenase/biosynthesis

KW - Animals

KW - Male

KW - Female

KW - Mice

KW - Mice, Inbred BALB C

KW - Rats

KW - Rats, Wistar

KW - Antigens, CD4/chemistry/immunology

KW - Antigens, CD8/chemistry/immunology

KW - Dopamine beta-Hydroxylase/biosynthesis

KW - Dynorphins/biosynthesis

KW - Endorphins/biosynthesis

KW - Enkephalin, Methionine/biosynthesis

KW - Liver/cytology/innervation/metabolism

KW - Nerve Fibers/chemistry

KW - Neuroimmunomodulation

KW - Receptors, Opioid/biosynthesis

KW - Sympathetic Nervous System/cytology/metabolism

KW - T-Lymphocytes/cytology/immunology/metabolism

KW - Tyrosine 3-Monooxygenase/biosynthesis

M3 - SCORING: Journal article

VL - 120

SP - 213

EP - 221

JO - HISTOCHEM CELL BIOL

JF - HISTOCHEM CELL BIOL

SN - 0948-6143

IS - 3

M1 - 3

ER -