The non-neuronal cholinergic system in peripheral blood cells: effects of nicotinic and muscarinic receptor antagonists on phagocytosis, respiratory burst and migration.
Peripheral blood cells express the complete non-neuronal cholinergic system. For example synthesis of acetylcholine and nicotinic as well muscarinic receptors have been demonstrated in leucocytes isolated from human peripheral blood. In the present experiments mononuclear cells and granulocytes were isolated from the peripheral blood to investigate content and synthesis of acetylcholine as well as phenotypic functions like respiratory burst, phagocytosis and migration. Mononuclear cells (T-cells and monocytes) contained 0.36 pmol/10(6) cells acetylcholine, whereas acetylcholine content in granulocytes was 100-fold lower. Acetylcholine synthesis amounted to 23.2+/-4.7 nmol/mg protein/h and 2.90+/-0.84 in CD15+ (granulocytes) and CD3+ cells (T-lymphocytes), respectively. Neither atropine (blockade of muscarinic receptors) nor tubocurarine (blockade of nicotinic receptors) exerted an effect on the respiratory burst. Tubocurarine (30 muM), alone or in combination with atropine (1 microM), reduced phagocytosis in granulocytes by 13% and 19%, respectively (p<0.05). Spontaneous transwell migration of granulocytes was doubled by tubocurarine combined with atropine (p>0.05). Also alpha-bungarotoxin (10 microg/ml) enhanced spontaneous granulocyte migration, but hexamethonium (300 microM) was without effect. The present experiments demonstrate a cholinergic modulation of immune functions in peripheral leucocytes under in vitro conditions, i.e. in the absence of a neuronal innervation. Blockade of nicotine receptors (alpha1 muscular subtype) facilitates spontaneous migration of granulocytes.
Neumann
Stefanie
S
Institute of Pathology, University Hospital, Johannes Gutenberg University, D-55101 Mainz, Germany.
Razen
Michael
M
Habermehl
Pirmin
P
Meyer
Claudius U
CU
Zepp
Fred
F
Kirkpatrick
Charles James
CJ
Wessler
Ignaz
I
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D014403:Tubocurarine / Q000494:pharmacology
D002038:Bungarotoxins; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D018738:Hexamethonium; D001285:Atropine; D000109:Acetylcholine; D014403:Tubocurarine