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The human carotid body releases acetylcholine, ATP and cytokines during hypoxia
Author(s) -
Kåhlin Jessica,
Mkrtchian Souren,
Ebberyd Anette,
HammarstedtNordenvall Lalle,
Nordlander Britt,
Yoshitake Takashi,
Kehr Jan,
Prabhakar Nanduri,
Poellinger Lorenz,
Fagerlund Malin Jonsson,
Eriksson Lars I.
Publication year - 2014
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2014.078873
Subject(s) - carotid body , hypoxia (environmental) , immune system , reflex , medicine , endocrinology , cytokine , acetylcholine , chemoreceptor , glomus cell , receptor , biology , immunology , carotid arteries , chemistry , organic chemistry , oxygen
New FindingsWhat is the central question of this study? Data on human carotid body (CB) function are limited. The aim of this study was therefore to investigate whether the human CB releases acetylcholine, ATP or cytokines during hypoxia.What is the main finding and its importance? Using human CBs, we demonstrate hypoxia‐induced acetylcholine and ATP release, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. Moreover, the human CB releases cytokines upon hypoxia and expresses cytokine receptors as well as hypoxia‐inducible factor proteins HIF‐1α and HIF‐2α in glomus cells, indicating their role in immune signalling and oxygen sensing, respectively, in accordance with previous animal data.Studies on experimental animals established that the carotid bodies are sensory organs for detecting arterial blood O 2 levels and that the ensuing chemosensory reflex is a major regulator of cardiorespiratory functions during hypoxia. However, little information is available on the human carotid body responses to hypoxia. The present study was performed on human carotid bodies obtained from surgical patients undergoing elective head and neck cancer surgery. Our results show that exposing carotid body slices to hypoxia for a period as brief as 5 min markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia for 1 h induces an increased release of interleukin (IL)‐1β, IL‐4, IL‐6, IL‐8 and IL‐10. Immunohistochemical analysis revealed that type 1 cells of the human carotid body express an array of cytokine receptors as well as hypoxia‐inducible factor‐1α and hypoxia‐inducible factor‐2α. Taken together, these results demonstrate that ACh and ATP are released from the human carotid body in response to hypoxia, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. The finding that the human carotid body releases cytokines in response to hypoxia adds to the growing body of information suggesting that the carotid body may play a role in detecting inflammation, providing a link between the immune system and the nervous system.