Asthmatic allergen inhalation sensitises carotid bodies to lysophosphatidic acid

Journal of Neuroinflammation

Richard J. A. Wilson¹  Arijit Roy¹  Nicholas G. Jendzjowsky² 

[1] Department of Physiology and Pharmacology, Alberta Children’s Hospital Research Institute, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Rm 203 Heritage Medical Research Building, 3330 Hospital Drive NW, T2N 4N1, Calgary, Alberta, Canada;Department of Respiratory Medicine and Exercise Physiology, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Rm 209 Martin Research Building, 1124 West Carson Street, 90502, Torrance, CA, USA;

关键词: TRPV1;    Lysophosphatidic acid;    Asthma;    Carotid body;    Petrosal ganglion;    Allergen;    Neuro-immune;    Neuroimmunology;   

DOI  :  10.1186/s12974-021-02241-9

来源: Springer

【 摘 要 】

The carotid bodies are multimodal sensors that regulate various autonomic reflexes. Recent evidence demonstrates their role in immune reflex regulation. Our previous studies using the allergen (ovalbumin) sensitised and exposed Brown Norway rat model of asthma suggest that carotid bodies mediate asthmatic bronchoconstriction through a lysophosphatidic acid (LPA) receptor (LPAr)-protein kinase C epsilon (PKCε)-transient receptor potential vanilloid one channel (TRPV1) pathway. Whilst naïve carotid bodies respond to LPA, whether their response to LPA is enhanced in asthma is unknown. Here, we show that asthmatic sensitisation of Brown Norway rats involving repeated aerosolised allergen challenges over 6 days, results in an augmentation of the carotid bodies’ acute sensitivity to LPA. Increased expression of LPAr in the carotid bodies and petrosal ganglia likely contributed to this sensitivity. Importantly, allergen sensitisation of the carotid bodies to LPA did not alter their hypoxic response, nor did hypoxia augment LPA sensitivity acutely. Our data demonstrate the ability of allergens to sensitise the carotid bodies, highlighting the likely role of the carotid bodies and blood-borne inflammatory mediators in asthma.

【 授权许可】

CC BY