Asthmatic allergen inhalation sensitises carotid bodies to lysophosphatidic acid

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 (PKC epsilon)-transient receptor potential vanilloid one channel (TRPV1) pathway. Whilst naive 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.

Automated summary

Carotid bodies are multimodal sensors that regulate autonomic reflexes and are also involved in immune reflex regulation. Studies on asthma models suggest that carotid bodies mediate asthmatic bronchoconstriction through the LPA-LPAr-PKCε-TRPV1 pathway. Allergen sensitization can enhance the acute sensitivity of carotid bodies to LPA, possibly involving increased expression of LPAr. This allergen-induced sensitization of carotid bodies highlights their potential role in asthma, along with blood-borne inflammatory mediators.