Galioto GB (ed): Tonsils: A Clinically Oriented Update. Adv Otorhinolaryngol. Basel, Karger, 1992, vol 47, pp 28-31
Autonomic Nervous System in the Tonsil Koichi Tomoda, Norio Maeda, Kageyuki Kozuki, Kazuo Sato, Nobuo Kubo, Masanori Kitajiri, Toshio Yamashita, Tadami Kumazawa Department of Otolaryngology, Kansai Medical University, Fumizonocho, Moriguchi, Osaka, Japan
Concerning the participation of autonomic nerves in the tonsils, the autonomic nerves have long been assumed to play an important role when the relation between the tonsillar focus and the whole body is considered, or when shock at tonsillectomy is associated with Reilly's phenomenon, and it has attracted a great deal of interest. In the present study, we investigated the anatomic distribution of autonomic nerve fibers and its terminals in the tonsils. Material and Methods Twenty human palatine tonsils, obtained from patients aged from 6 to 8 years who had undergone tonsillectomy, were prepared for the histologic examinations. Adrenergic nerve fibers were observed by the glyoxylic acid method [1], while cholinergic nerves were investigated using acetylcholinesterase (AchE) by the method of Karnovsky and Roots [2]. Neuropeptide-containing nerve fibers, such as tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and calcitonin gene-related peptide (CGRP), were immunohistochemically investigated by the ABC method. Adrenergic nerve terminals innervated in the rabbit's palatine tonsils were observed using an electron microscope with a pretreatment of an injection of 5-hydroxydopamine (5-0HDA).
Results
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The distribution of adrenergic, cholinergic and neuropeptide-containing nerve fibers in the tonsil are shown in table 1. Adrenergic nerve fibers
29
Autonomic Nervous System in the Tonsil
Table 1. Distribution of adrenergic, cholinergic or neuropeptidergic nerve fibers in tonsil AD
AchE
TH
NPY
VIP
CGRP SP
SOM
Capsule
+
+
++
++
++
+
+
+
Septum
++
+
++
++
++
+
+
+
Follicle
+
+
+
+
+
Glands
+
+
+
+ = < 4 fibers; ++
=
+
Epithelium ++
with a varicose appearance were seen closely associated with the vessel walls in the hilus and travelled, with a decreasing number, through the septum to the parafollicular region. The strong activity of AchE was found around the vessel walls located in the tonsillar capsule and septum. The fine nerve fibers containing AchE activity distributed to the parafollicular spaces. Of neuropeptide-containing fibers, a large number of fibers immunoreactive to TH or VIP were dominantly distributed around the vessels in the hilus and septum, and less distributed in the parafollicular spaces. Those individual nerve fibers showed a varicose appearance. An abundant distribution of VIP fibers was specially seen in the para-acinal region of the Weber's glands. The localization of NPY-immunoreactive fibers was similar to those of TH or VIP with an exception of distributing to the glands. The nerve supply of SP, SOM or CGRP was less as compared to those of three fibers mentioned. However, SOM fibers were only seen in the germinal center. None of the fibers were distributed to the epithelium. Adrenergic nerve terminals were characterized by the presence of small and large dense-cored granular vesicles which contained 5-0HDA, while cholinergic nerve terminals had only small clear synaptic vesicles (agranular vesicles). Both adrenergic or cholinergic nerve terminals were mainly located in the hilus, just beneath the smooth muscle layer of the arteries and in the preacinal region of the Weber's glands (fig. 1). None of the nerve terminals were found in the parafollicular regions or germinal centers.
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> 5 fibers in 200 X 200 j.lm2.
Tomoda/Maeda/Kozuki/Sato/Kubo/Kitajiri/Yamashita/Kumazawa
30
b
b Fig. 1. a Adrenergic (Ad) and cholinergic nerve terminal (Cho) are seen close to the gland (G) and vessel (V). b Adrenergic nerve terminals are characterized by the presence of small (SCV) and large dense-cored granular vesicles (LCV) which contained 5OHDA.
The sympathetic nerves containing TH and NPY distributed in the tonsil originate from the superior cervical ganglion, and its neurotransmitter is noradrenaline. The parasympathetic nerves containing VIP distributed in the tonsil originate from the sphenopalatine ganglion, and its neurotransmitter is acetylcholine. They are thought to be involved in direct information transmission from the central nervous system to the tonsils. Adrenergic or cholinergic receptors are known to be present on thymic, splenic and tonsillar lymphocytes [3-5]. VIP receptors have been reported on specific lymphocytes of the peripheral blood [6]. With these
Downloaded by: Université de Paris 193.51.85.197 - 1/12/2020 11:45:34 PM
Discussion
Autonomic Nervous System in the Tonsil
31
communications, the functional significance of an autonomic nervous system may include not only regulation of blood flow in the tonsils but also of lymphocyte development and immune responses. The afferent (sensory) nerves containing SP, SOM and CGRP located in the tonsils originate from the trigeminal or the dorsal root of the cervical ganglion and directly transmit information, arising from inflammatory or immune reactions, from lymphoid tissues to the central nervous system. They may participate in the local regulation of blood flow or the vascular permeability by an axonal collateral. The quantitative analysis of norepinephrine in the tonsillar tissues revealed that the value of norepinephrine was higher in the cases of habitual tonsillitis than those of simple hypertrophy [7]. Our results may require further studies on the neural-immune interactions in the tonsils.
References
2 3 4
5
6
7
Lindvall 0, Bjorklund A: The glyoxylic acid fluorescence histochemical method: a detailed account of the methodology for the visualization of central catecholamine neurons. Histochemistry 1974;39:97-127. Karnovsky MJ, Roots L: A 'direct coloring' thiocholine method for cholinesterases. J Histochem Cytochem 1964; 12:219-221. Felten SY, Felten DL, Bellinger DL, et al: Noradrenergic sympathetic innervation of lymphoid organs. Prog Allergy 1988;43: 14-36. Richman DP, Amason BGW: Nicotinic acetylcholine receptor; evidence for a functional distinct receptor on human lymphocytes. Proc Nat! Acad Sci USA 1979;76: 4632-4635. Yamashita T, Kumazawa H, Kozuki K, Amano H, Tomoda K, Kumazawa T: Autonomic nervous system in human palatine tonsil. Acta OtolaryngoI1984(suppI416): 63-71. O'Dorsio MS, Shannon BT, Fleshman DJ, et al: Identification of high affinity receptors for vasoactive intestinal peptide on human lymphocytes of B cell lineage. J Immunol 1989;142:3533-3536. Kozuki K: Various tonsillitis and sympathetic nerves - A study of chemical neurotransmitters. Pract Otol (Kyoto) 1987;80:299-312.
Dr. Koichi Tomoda, Department of Otolaryngology, Kansai Medical University, Fumizonocho, Moriguchi, Osaka 570 (Japan)
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b2
Autonomic Nervous System in the Tonsil Koichi Tomoda, Norio Maeda, Kageyuki Kozuki, Kazuo Sato, Nobuo Kubo, Masanori Kitajiri, Toshio Yamashita, Tadami Kumazawa Department of Otolaryngology, Kansai Medical University, Fumizonocho, Moriguchi, Osaka, Japan
Concerning the participation of autonomic nerves in the tonsils, the autonomic nerves have long been assumed to play an important role when the relation between the tonsillar focus and the whole body is considered, or when shock at tonsillectomy is associated with Reilly's phenomenon, and it has attracted a great deal of interest. In the present study, we investigated the anatomic distribution of autonomic nerve fibers and its terminals in the tonsils. Material and Methods Twenty human palatine tonsils, obtained from patients aged from 6 to 8 years who had undergone tonsillectomy, were prepared for the histologic examinations. Adrenergic nerve fibers were observed by the glyoxylic acid method [1], while cholinergic nerves were investigated using acetylcholinesterase (AchE) by the method of Karnovsky and Roots [2]. Neuropeptide-containing nerve fibers, such as tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and calcitonin gene-related peptide (CGRP), were immunohistochemically investigated by the ABC method. Adrenergic nerve terminals innervated in the rabbit's palatine tonsils were observed using an electron microscope with a pretreatment of an injection of 5-hydroxydopamine (5-0HDA).
Results
Downloaded by: Université de Paris 193.51.85.197 - 1/12/2020 11:45:34 PM
The distribution of adrenergic, cholinergic and neuropeptide-containing nerve fibers in the tonsil are shown in table 1. Adrenergic nerve fibers
29
Autonomic Nervous System in the Tonsil
Table 1. Distribution of adrenergic, cholinergic or neuropeptidergic nerve fibers in tonsil AD
AchE
TH
NPY
VIP
CGRP SP
SOM
Capsule
+
+
++
++
++
+
+
+
Septum
++
+
++
++
++
+
+
+
Follicle
+
+
+
+
+
Glands
+
+
+
+ = < 4 fibers; ++
=
+
Epithelium ++
with a varicose appearance were seen closely associated with the vessel walls in the hilus and travelled, with a decreasing number, through the septum to the parafollicular region. The strong activity of AchE was found around the vessel walls located in the tonsillar capsule and septum. The fine nerve fibers containing AchE activity distributed to the parafollicular spaces. Of neuropeptide-containing fibers, a large number of fibers immunoreactive to TH or VIP were dominantly distributed around the vessels in the hilus and septum, and less distributed in the parafollicular spaces. Those individual nerve fibers showed a varicose appearance. An abundant distribution of VIP fibers was specially seen in the para-acinal region of the Weber's glands. The localization of NPY-immunoreactive fibers was similar to those of TH or VIP with an exception of distributing to the glands. The nerve supply of SP, SOM or CGRP was less as compared to those of three fibers mentioned. However, SOM fibers were only seen in the germinal center. None of the fibers were distributed to the epithelium. Adrenergic nerve terminals were characterized by the presence of small and large dense-cored granular vesicles which contained 5-0HDA, while cholinergic nerve terminals had only small clear synaptic vesicles (agranular vesicles). Both adrenergic or cholinergic nerve terminals were mainly located in the hilus, just beneath the smooth muscle layer of the arteries and in the preacinal region of the Weber's glands (fig. 1). None of the nerve terminals were found in the parafollicular regions or germinal centers.
Downloaded by: Université de Paris 193.51.85.197 - 1/12/2020 11:45:34 PM
> 5 fibers in 200 X 200 j.lm2.
Tomoda/Maeda/Kozuki/Sato/Kubo/Kitajiri/Yamashita/Kumazawa
30
b
b Fig. 1. a Adrenergic (Ad) and cholinergic nerve terminal (Cho) are seen close to the gland (G) and vessel (V). b Adrenergic nerve terminals are characterized by the presence of small (SCV) and large dense-cored granular vesicles (LCV) which contained 5OHDA.
The sympathetic nerves containing TH and NPY distributed in the tonsil originate from the superior cervical ganglion, and its neurotransmitter is noradrenaline. The parasympathetic nerves containing VIP distributed in the tonsil originate from the sphenopalatine ganglion, and its neurotransmitter is acetylcholine. They are thought to be involved in direct information transmission from the central nervous system to the tonsils. Adrenergic or cholinergic receptors are known to be present on thymic, splenic and tonsillar lymphocytes [3-5]. VIP receptors have been reported on specific lymphocytes of the peripheral blood [6]. With these
Downloaded by: Université de Paris 193.51.85.197 - 1/12/2020 11:45:34 PM
Discussion
Autonomic Nervous System in the Tonsil
31
communications, the functional significance of an autonomic nervous system may include not only regulation of blood flow in the tonsils but also of lymphocyte development and immune responses. The afferent (sensory) nerves containing SP, SOM and CGRP located in the tonsils originate from the trigeminal or the dorsal root of the cervical ganglion and directly transmit information, arising from inflammatory or immune reactions, from lymphoid tissues to the central nervous system. They may participate in the local regulation of blood flow or the vascular permeability by an axonal collateral. The quantitative analysis of norepinephrine in the tonsillar tissues revealed that the value of norepinephrine was higher in the cases of habitual tonsillitis than those of simple hypertrophy [7]. Our results may require further studies on the neural-immune interactions in the tonsils.
References
2 3 4
5
6
7
Lindvall 0, Bjorklund A: The glyoxylic acid fluorescence histochemical method: a detailed account of the methodology for the visualization of central catecholamine neurons. Histochemistry 1974;39:97-127. Karnovsky MJ, Roots L: A 'direct coloring' thiocholine method for cholinesterases. J Histochem Cytochem 1964; 12:219-221. Felten SY, Felten DL, Bellinger DL, et al: Noradrenergic sympathetic innervation of lymphoid organs. Prog Allergy 1988;43: 14-36. Richman DP, Amason BGW: Nicotinic acetylcholine receptor; evidence for a functional distinct receptor on human lymphocytes. Proc Nat! Acad Sci USA 1979;76: 4632-4635. Yamashita T, Kumazawa H, Kozuki K, Amano H, Tomoda K, Kumazawa T: Autonomic nervous system in human palatine tonsil. Acta OtolaryngoI1984(suppI416): 63-71. O'Dorsio MS, Shannon BT, Fleshman DJ, et al: Identification of high affinity receptors for vasoactive intestinal peptide on human lymphocytes of B cell lineage. J Immunol 1989;142:3533-3536. Kozuki K: Various tonsillitis and sympathetic nerves - A study of chemical neurotransmitters. Pract Otol (Kyoto) 1987;80:299-312.
Dr. Koichi Tomoda, Department of Otolaryngology, Kansai Medical University, Fumizonocho, Moriguchi, Osaka 570 (Japan)
Downloaded by: Université de Paris 193.51.85.197 - 1/12/2020 11:45:34 PM
b2
