The Human Carotid Body Gene Expression and Function in Signaling of Hypoxia and Inflammation

  • Jessica KåhlinEmail author
  • Souren Mkrtchian
  • Anette Ebberyd
  • Lars I Eriksson
  • Malin Jonsson Fagerlund
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 860)


Although animal carotid body oxygen sensing and signaling has been extensively investigated, the human carotid body remains essentially uncharacterized. Therefore, we aimed to study the human carotid body in terms of morphology, global and specific expression of sensing and signaling genes as well as inflammatory genes. The human carotid body response to brief or prolonged hypoxia was studied in carotid body slices from adult surgical patients and ACh, ATP and cytokine release was analyzed. We demonstrate that the human carotid body expresses key oxygen sensing and signaling genes in similarity with animal carotid bodies with a few diverging data. The human carotid body moreover shows enrichment of genes in the inflammatory response and releases pro and anti-inflammatory cytokines in response to prolonged hypoxia. In response to acute hypoxia the human carotid body releases ACh and ATP and we thus translate previous findings in animal models to human tissue. We conclude that by releasing pro- and anti-inflammatory cytokines during hypoxia the human carotid body displays a structural and functional capacity to participate in sensing and mediating systemic inflammation.


Carotid body Hypoxia Neurotransmitter ACh ATP Inflammation Cytokine Human Gene expression 


  1. Balbir A, Lee H, Okumura M, Biswal S, Fitzgerald RS, Shirahata M (2007) A search for genes that may confer divergent morphology and function in the carotid body between two strains of mice. Am J Physiol Lung Cell Mol Physiol 292(3):L704–L715PubMedCrossRefGoogle Scholar
  2. Diogo LN, Monteiro EC (2014) The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions. Front Physiol 5:361. doi: 10.3389/fphys.2014.00361 PubMedCrossRefPubMedCentralGoogle Scholar
  3. Fagerlund MJ, Kahlin J, Ebberyd A, Schulte G, Mkrtchian S, Eriksson LI (2010) The human carotid body: expression of oxygen sensing and signaling genes of relevance for anesthesia. Anesthesiology 113(6):1270–1279PubMedCrossRefGoogle Scholar
  4. Fernandez R, Gonzalez S, Rey S et al (2008) Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha. Exp Physiol 93(7):892–907. doi: 10.1113/expphysiol.2008.041152 PubMedCrossRefGoogle Scholar
  5. Fernandez R, Nardocci G, Simon F et al (2011) Lipopolysaccharide signaling in the carotid chemoreceptor pathway of rats with sepsis syndrome. Respir Physiol Neurobiol 175(3):336–348. doi: 10.1016/j.resp.2010.12.014 PubMedCrossRefGoogle Scholar
  6. Fletcher EC, Lesske J, Behm R, Miller CC 3rd, Stauss H, Unger T (1992) Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea. J Appl Physiol (Bethesda, Md : 1985) 72(5):1978–1984Google Scholar
  7. Fung ML (2014) Pathogenic roles of the carotid body inflammation in sleep apnea. Mediators Inflamm 2014:354279. doi: 10.1155/2014/354279 PubMedCrossRefPubMedCentralGoogle Scholar
  8. Ganfornina MD, Perez-Garcia MT, Gutierrez G et al (2005) Comparative gene expression profile of mouse carotid body and adrenal medulla under physiological hypoxia. J Physiol 566(Pt 2):491–503PubMedCrossRefPubMedCentralGoogle Scholar
  9. Kahlin J, Mkrtchian S, Ebberyd A et al (2014) The human carotid body releases acetylcholine, ATP and cytokines during hypoxia. Exp Physiol 99(8):1089–1098. doi: 10.1113/expphysiol.2014.078873 PubMedCrossRefGoogle Scholar
  10. Kumar P, Prabhakar NR (2012) Peripheral chemoreceptors: function and plasticity of the carotid body. Compr Physiol 2(1):141–219. doi: 10.1002/cphy.c100069 PubMedPubMedCentralGoogle Scholar
  11. Lam SY, Tipoe GL, Liong EC, Fung ML (2008) Chronic hypoxia upregulates the expression and function of proinflammatory cytokines in the rat carotid body. Histochem Cell Biol 130(3):549–559. doi: 10.1007/s00418-008-0437-4 PubMedCrossRefGoogle Scholar
  12. Milsom WK, Burleson ML (2007) Peripheral arterial chemoreceptors and the evolution of the carotid body. Respir Physiol Neurobiol 157(1):4–11. doi: 10.1016/j.resp.2007.02.007 PubMedCrossRefGoogle Scholar
  13. Mkrtchian S, Kahlin J, Ebberyd A et al (2012) The human carotid body transcriptome with focus on oxygen sensing and inflammation–a comparative analysis. J Physiol 590(Pt 16):3807–3819. doi: 10.1113/jphysiol.2012.231084 PubMedCrossRefPubMedCentralGoogle Scholar
  14. Nurse CA (2005) Neurotransmission and neuromodulation in the chemosensory carotid body. Auton Neurosci 120(1–2):1–9PubMedCrossRefGoogle Scholar
  15. Ortega-Saenz P, Pardal R, Levitsky K et al (2013) Cellular properties and chemosensory responses of the human carotid body. J Physiol. doi: 10.1113/jphysiol.2013.263657 PubMedPubMedCentralGoogle Scholar
  16. Prabhakar NR (2006) O2 sensing at the mammalian carotid body: why multiple O2 sensors and multiple transmitters? Exp Physiol 91(1):17–23PubMedCrossRefGoogle Scholar
  17. Prabhakar NR, Semenza GL (2012) Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. Physiol Rev 92(3):967–1003. doi: 10.1152/physrev.00030.2011 PubMedCrossRefPubMedCentralGoogle Scholar
  18. Ross FA, Rafferty JN, Dallas ML et al (2011) Selective expression in carotid body type I cells of a single splice variant of the large conductance calcium- and voltage-activated potassium channel confers regulation by AMP-activated protein kinase. J Biol Chem 286(14):11929–11936. doi: 10.1074/jbc.M110.189779 PubMedCrossRefPubMedCentralGoogle Scholar
  19. Shirahata M, Balbir A, Otsubo T, Fitzgerald RS (2007) Role of acetylcholine in neurotransmission of the carotid body. Respir Physiol Neurobiol 157(1):93–105PubMedCrossRefGoogle Scholar
  20. Tang GJ, Kou YR, Lin YS (1998) Peripheral neural modulation of endotoxin-induced hyperventilation. Crit Care Med 26(9):1558–1563PubMedCrossRefGoogle Scholar
  21. Zhang XJ, Wang X, Xiong LZ, Fan J, Duan XL, Wang BR (2007) Up-regulation of IL-1 receptor type I and tyrosine hydroxylase in the rat carotid body following intraperitoneal injection of IL-1beta. Histochem Cell Biol 128(6):533–540. doi:10.1007/s00418-007-0346-y PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Jessica Kåhlin
    • 1
    Email author
  • Souren Mkrtchian
    • 1
  • Anette Ebberyd
    • 1
  • Lars I Eriksson
    • 1
  • Malin Jonsson Fagerlund
    • 1
  1. 1.Department of Anesthesiology, Surgical Services and Intensive Care Medicine, Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care MedicineKarolinska University Hospital and Karolinska InstitutetStockholmSweden

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