Up-regulation of IL-1 receptor type I and tyrosine hydroxylase in the rat carotid body following intraperitoneal injection of IL-1β

Various heme-containing proteins have been proposed as primary molecular O2 sensors for hypoxia-sensitive type I cells in the mammalian carotid body. One set of data in particular supports the involvement of a cytochrome b NADPH oxidase that is commonly found in neutrophils. Subunits of this enzyme have been immunocytochemically localized in type I cells, and diphenyleneiodonium, an inhibitor of the oxidase, increases carotid body chemoreceptor activity. The present study evaluated immunocytochemical and functional properties of carotid bodies from normal mice and from mice with a disrupted gp91 phagocytic oxidase (gp91 phox ) DNA sequence gene knockout (KO), a gene that codes for a subunit of the neutrophilic form of NADPH oxidase. Immunostaining for tyrosine hydroxylase, a signature marker antigen for type I cells, was found in groups or lobules of cells displaying morphological features typical of the O2-sensitive cells in other species, and the incidence of tyrosine hydroxylase-immunopositive cells was similar in carotid bodies from both strains of mice. Studies of whole cell K+currents also revealed identical current-voltage relationships and current depression by hypoxia in type I cells dissociated from normal vs. KO animals. Likewise, hypoxia-evoked increases in intracellular Ca2+ concentration were not significantly different for normal and KO type I cells. The whole organ response to hypoxia was evaluated in recordings of carotid sinus nerve activity in vitro. In these experiments, responses elicited by hypoxia and by the classic chemoreceptor stimulant nicotine were also indistinguishable in normal vs. KO preparations. Our data demonstrate that carotid body function remains intact after sequence disruption of the gp91 phox gene. These findings are not in accord with the hypothesis that the phagocytic form of NADPH oxidase acts as a primary O2 sensor in arterial chemoreception.

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Immunohistochemical Characteristics of the Human Carotid Body in the Antenatal and Postnatal Periods of Development

International Journal of Molecular Sciences ◽

10.3390/ijms22158222 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8222

Author(s):

Dmitry Otlyga ◽

Ekaterina Tsvetkova ◽

Olga Junemann ◽

Sergey Saveliev

Keyword(s):

Tyrosine Hydroxylase ◽

Carotid Body ◽

Nerve Fibers ◽

Individual Development ◽

Endocrine Function ◽

Type I ◽

Type I Cells ◽

Carotid Bodies ◽

I Cells ◽

Human Carotid

The evolutionary and ontogenetic development of the carotid body is still understudied. Research aimed at studying the comparative morphology of the organ at different periods in the individual development of various animal species should play a crucial role in understanding the physiology of the carotid body. However, despite more than two centuries of study, the human carotid body remains poorly understood. There are many knowledge gaps in particular related to the antenatal development of this structure. The aim of our work is to study the morphological and immunohistochemical characteristics of the human carotid body in the antenatal and postnatal periods of development. We investigated the human carotid bodies from 1 embryo, 20 fetuses and 13 adults of different ages using samples obtained at autopsy. Immunohistochemistry revealed expression of βIII-tubulin and tyrosine hydroxylase in the type I cells and nerve fibers at all periods of ontogenesis; synaptophysin and PGP9.5 in the type I cells in some of the antenatal cases and all of the postnatal cases; 200 kDa neurofilaments in nerve fibers in some of the antenatal cases and all of the postnatal cases; and GFAP and S100 in the type II cells and Schwann cells in some of the antenatal cases and all of the postnatal cases. A high level of tyrosine hydroxylase in the type I cells was a distinctive feature of the antenatal carotid bodies. On the contrary, in the type I cells of adults, the expression of tyrosine hydroxylase was significantly lower. Our data suggest that the human carotid body may perform an endocrine function in the antenatal period, while in the postnatal period of development, it loses this function and becomes a chemosensory organ.

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Strong Expression of Interleukin-1 Receptor Type I in the Rat Carotid Body

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540205001213 ◽

2002 ◽

Vol 50 (12) ◽

pp. 1677-1684 ◽

Cited By ~ 49

Author(s):

Xi Wang ◽

Bai-Ren Wang ◽

Xiao-Li Duan ◽

Ping Zhang ◽

Yu-Qiang Ding ◽

...

Keyword(s):

Western Blotting ◽

Carotid Body ◽

Interleukin 1 ◽

Underlying Mechanism ◽

Receptor Type ◽

Type I ◽

Glomus Cells ◽

Almost All ◽

The Brain ◽

Key Questions

One of the unsolved key questions in neuroimmunomodulation is how peripheral immune signals are transmitted to the brain. It has been reported that the vagus might play a role in this regard. The underlying mechanism for this immune system-to-brain communication route is related to the binding of cytokines, such as interleukin (IL)-1β originating from activated immune cells, to their receptors in glomus cells of the vagal paraganglia. The existence of IL-1 receptor type I (IL-1RI) in vagal paraganglia has been proved. On the basis of these studies, a hypothesis is raised that the carotid body, as the largest paraganglion, might play a similar role to that of its abdominal partner. In this study we examined the distribution of IL-1RI in the carotid body by immunohistochemistry (IHC) and Western blotting techniques. The IHC results showed that almost all glomus cells in the carotid body displayed strong IL-1RI immunoreactivity. The IL-1RI-immunoreactive products were localized in the cytoplasm, nucleus, and cell membrane of the glomus cells. The Western blotting results also confirmed the existence of IL-1RI in both membranous and cytoplasmic elements of the carotid body. These results imply that the carotid body not only serves as a chemoreceptor for modulation of cardiorespiratory performance, as traditionally recognized, but also acts as a cytokine chemorereceptor for sensing immune signals.

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Mechanisms of O2 Sensing in the Carotid Body in Comparison With Other O2-Sensing Cells

Physiology ◽

10.1152/physiologyonline.1995.10.5.211 ◽

1995 ◽

Vol 10 (5) ◽

pp. 211-216 ◽

Cited By ~ 5

Author(s):

H Acker ◽

D Xue

Keyword(s):

Gene Expression ◽

Tyrosine Hydroxylase ◽

Potassium Channel ◽

Carotid Body ◽

Type I ◽

Open Probability ◽

Signal Cascade ◽

Sensor Protein ◽

I Cells ◽

O2 Sensing

An NAD(P)H oxidase-generating H2O2 dependent on PO2 is proposed as an O2 sensor protein in type I cells of the carotid body, regulating potassium channel open probability as well as tyrosine hydroxylase gene expression. The proposed signal cascade also is important in other O2-sensing cells.

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Immunohistochemical features of the human carotid body

CLINICAL AND EXPERIMENTAL MORPHOLOGY ◽

10.31088/cem2020.9.3.61-67 ◽

2020 ◽

Vol 9 (3) ◽

pp. 61-67

Author(s):

D.A. Otlyga ◽

O.A. Junemann ◽

E.G. Tsvetkova ◽

K.R. Gorokhov ◽

S.V. Saveliev

Keyword(s):

Tyrosine Hydroxylase ◽

Carotid Body ◽

Molecular Genetic ◽

Nerve Fibers ◽

Laboratory Animals ◽

Type I ◽

Nuclear Staining ◽

Human Organ ◽

Rats And Mice ◽

Human Carotid

Introduction. The carotid body is a chemoreceptor organ and the initial link of the reflex regulation of car-diovascular and respiratory systems. However, molecular genetic and immunohistochemical characteristics of the human carotid body remains underinvestigated. Although there are numerous studies of the second half of the 20th century devoted to the classical light-optical histology of the human organ, the immunohis-tochemical investigations are very few. The aim of our study was to clarify immunohistochemical features of the human carotid body in comparison with those of the most commonly used laboratory animals. Materials and methods. The study was performed on 10 carotid bodies of the adult human of different ages of both sexes using immunoperoxidase labeling with antibodies to bIII-tubulin, tyrosine hydroxylase, syn-aptophysin, PGP9.5, neurofilaments 200kDa, S100, and GFAP. Results. Nerve fibers passing between the lobules, as well as entering them, were positive for bIII-tubulin, tyrosine hydroxylase, PGP9.5 and neurofilaments. Type I cells had cytoplasmic reaction for bIII-tubulin and synaptophysin as well as cytoplasmic and nuclear staining for PGP9.5. At the same time, they had weaker reaction for tyrosine hydroxylase. Type II cells were positive for GFAP and S100. Conclusion. Immunohistochemical characteristics of the human carotid body were similar to those of rats and mice. The human carotid body cells and nerve fibers showed the same distribution of PGP9.5, bIII-tubulin, synaptophysin, neurofilaments, GFAP and S100 as rat and mouse carotid body cells. However, human carotid body reaction for tyrosine hydroxylase was much lower, which may indicate a smaller amount of synthesized catecholamines compared to the carotid body in rats and mice. Keywords: human carotid body, immunohistochemistry, sympathoadrenal system, tyrosine hydroxylase

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