Abstract
The carotid body (CB), a neural-crest-derived organ and the main arterial chemoreceptor in mammals, is composed of clusters of cells called glomeruli. Each glomerulus contains neuron-like, O2-sensing glomus cells, which are innervated by sensory fibers of the petrosal ganglion and are located in close contact with a dense network of fenestrated capillaries. In response to hypoxia, glomus cells release transmitters to activate afferent fibers impinging on the respiratory and autonomic centers to induce hyperventilation and sympathetic activation. Glomus cells are embraced by interdigitating processes of sustentacular, glia-like, type II cells. The CB has an extraordinary structural plasticity, unusual for a neural tissue, as it can grow several folds its size in subjects exposed to sustained hypoxia (as for example in high altitude dwellers or in patients with cardiopulmonary diseases). CB growth in hypoxia is mainly due to the generation of new glomeruli and blood vessels. In recent years it has been shown that the adult CB contains a collection of quiescent multipotent stem cells, as well as immature progenitors committed to the neurogenic or the angiogenic lineages. Herein, we review the main properties of the different cell types in the CB germinal niche. We also summarize experimental data suggesting that O2-sensitive glomus cells are the master regulators of CB plasticity. Upon exposure to hypoxia, neurotransmitters and neuromodulators released by glomus cells act as paracrine signals that induce proliferation and differentiation of multipotent stem cells and progenitors, thus causing CB hypertrophy and an increased sensory output. Pharmacological modulation of glomus cell activity might constitute a useful clinical tool to fight pathologies associated with exaggerated sympathetic outflow due to CB overactivation.
Highlights
The carotid body (CB), a paired organ located in the bifurcation of the carotid artery, is the main and prototypical polymodal arterial chemoreceptor in mammals
Glomus cells are the O2-sensing elements in the CB; they contain abundant synaptic vesicles [4,5] with several neurotransmitters and neuropeptides, which are rapidly released in response to hypoxia to activate the afferent sensory fibers
Given the exquisite sensitivity of glomus cells to lowering O2 tension, it is logical to suggest that they must play a fundamental role in the adaptive growth of the whole organ in response to hypoxia and that substances released by glomus cells regulate the activity of stem cells and progenitors in the CB germinal niche
Summary
The carotid body (CB), a paired organ located in the bifurcation of the carotid artery, is the main and prototypical polymodal arterial chemoreceptor in mammals. A decline in arterial O2 tension is detected by CB O2-sensing cells, which rapidly (in few seconds) activate sensory fibers of the glossopharyngeal nerve impinging on neurons in the brainstem and autonomic centers to induce hyperventilation and increased heart rate. In this way, both O2 uptake and its distribution to the tissues are enhanced. Glomus cells are the O2-sensing elements in the CB; they contain abundant synaptic vesicles [4,5] with several neurotransmitters and neuropeptides (see below), which are rapidly released in response to hypoxia to activate the afferent sensory fibers. In addition to the two main cell types, the CB contains intermediate progenitors, abundant macrophages, and fat cells
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