The human carotid body releases cytokines, acetylcholine and ATP during hypoxia

Kåhlin, Jessica; Mkrtchian, Souren; Ebberyd, Anette; Lorenz, Patrick E.; Fagerlund, Jonsson M.; Eriksson, Lennart

doi:10.1097/00003643-201406001-00308

Cited by 4 publications

(9 citation statements)

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“…We have shown that human CB glomus cells have functional properties that are similar to their lower mammals counterparts (Kahlin et al 2014 ;Ortega-Saenz et al 2013 ). Although the relative size of the human CB parenchyma seems to be smaller than that of other non-primate mammalian species, CB progenitor cells and chemosensitive glomus cells appear to be preserved in human subjects of advanced age (Ortega-Saenz et al 2013 ).…”

Section: Discussionmentioning

confidence: 79%

“…16.3b, c ) that are within the range of those calculated for similar responses in rats or mice with the same methodology (Ortega-Saenz et al 2003 ;Piruat et al 2004 ). Besides catecholamines, recent experiments have also shown the release of ATP and acetylcholine form human glomus cells (Kahlin et al 2014 ), which, as in lower mammalian species (Zhang et al 2000 ), could be the mediators of the glomus cell-afferent fi ber synapse. Although the protocol designed to obtain dispersed cells from human CB is still susceptible to improvement, we were able to get some cultures of healthy isolated human glomus cells in which hypoxia-evoked a robust increase in cytosolic [Ca 2+ ].…”

Section: Cellular Responses To Hypoxiamentioning

confidence: 99%

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Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body

Ortega-Sáenz

Villadiego

Pardal

et al. 2015

Advances in Experimental Medicine and Biology

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The carotid body (CB) is a polymodal chemoreceptor that triggers the hyperventilatory response to hypoxia necessary for the maintenance of O(2) homeostasis essential for the survival of organs such as the brain or heart. Glomus cells, the sensory elements in the CB, are also sensitive to hypercapnia, acidosis and, although less generally accepted, hypoglycemia. Current knowledge on CB function is mainly based on studies performed on lower mammals, but the information on the human CB is scant. Here we describe the structure, neurotrophic properties, and cellular responses to hypoxia and hypoglycemia of CBs dissected from human cadavers. The adult CB parenchyma contains clusters of chemosensitive glomus (type I) and sustentacular (type II) cells as well as nestin-positive progenitor cells. This organ also expresses high levels of the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). GDNF production and the number of progenitor and glomus cells were preserved in the CBs of human subjects of advanced age. As reported for other mammalian species, glomus cells responded to hypoxia by external Ca(2+)-dependent increase of cytosolic [Ca(2+)] and quantal catecholamine release. Human glomus cells are also responsive to hypoglycemia and together the two stimuli, hypoxia and hypoglycemia, can potentiate each other's effects. The chemo-sensory responses of glomus cells are also preserved at an advanced age. Interestingly, a neurogenic niche similar to that recently described in rodents is also preserved in the adult human CB. These new data on the cellular and molecular physiology of the CB pave the way for future pathophysiological studies involving this organ in humans.

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Section: Discussionmentioning

confidence: 79%

Section: Cellular Responses To Hypoxiamentioning

confidence: 99%

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body

Ortega-Sáenz

Villadiego

Pardal

et al. 2015

Advances in Experimental Medicine and Biology

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“…Kåhlin et al . () found that brief hypoxic challenges enhanced the release of ACh and ATP fourfold, in comparison to the hyperoxic basal conditions (95% O 2 with 5% CO 2 ). Prolonged hypoxia increased the release of interleukin (IL)‐1 β , IL‐4, IL‐6, IL‐8 and IL‐10, while IL‐2, IL‐5 and tumour necrosis factor‐ α were undetected.…”

mentioning

confidence: 93%

“…In this issue of Experimental Physiology , Kåhlin et al . () studied the secretory responses to hypoxia in functional human carotid bodies. Without doubt, advances in our knowledge of the physiological mechanisms in the human carotid body have been limited by the difficulties inherent in obtaining fresh tissue samples.…”

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confidence: 99%

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Functional studies of acetylcholine, ATP and cytokine release from the human carotid body: the new frontier for oxygen chemoreception physiology

Iturriaga¹

2014

Experimental Physiology

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The carotid body: a physiologically relevant germinal niche in the adult peripheral nervous system

Sobrino

Annese

Navarro-Guerrero

et al. 2018

Cell. Mol. Life Sci.

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The carotid body (CB) is the principal arterial chemoreceptor that mediates the hyperventilatory response to hypoxia. Our understanding of CB function and its role in disease mechanisms has progressed considerably in the last decades, particularly in recent years. The sensory elements of the CB are the neuron-like glomus cells, which contain numerous transmitters and form synapses with afferent sensory fibers. The activation of glomus cells under hypoxia mainly depends on the modulation of O 2 -sensitive K + channels which leads to cell depolarization and the opening of Ca 2+ channels. This model of sensory transduction operates in all mammalian species studied thus far, including man. However, the molecular mechanisms underlying the modulation of ion channel function by changes in the O 2 level are as yet unknown. The CB plays a fundamental role in acclimatization to sustained hypoxia. Mice with CB atrophy or patients who have undergone CB resection due to surgical treatments show a marked intolerance to even mild hypoxia. CB growth under hypoxia is supported by the existence of a resident population of neural crest-derived stem cells of glia-like phenotype. These stem cells are not highly affected by exposure to low O 2 tension; however, there are abundant synapse-like contacts between the glomus cells and stem cells (chemoproliferative synapses), which may be needed to trigger progenitor cell proliferation and differentiation under hypoxia. CB hypo-or hyperactivation may also contribute to the pathogenesis of several prevalent human diseases.

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The human carotid body releases cytokines, acetylcholine and ATP during hypoxia

Cited by 4 publications

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Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body

Functional studies of acetylcholine, ATP and cytokine release from the human carotid body: the new frontier for oxygen chemoreception physiology

The carotid body: a physiologically relevant germinal niche in the adult peripheral nervous system

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