Role of Secreted Phospholipase A2 Group X in Airway Physiology
Asthma is a common chronic disease of the airways characterized by airway inflammation and airway dysfunction in the form of airway hyperresponsiveness (AHR) that occurs in response to a variety of allergic and non-allergic stimuli.
Researchers identified a specific phospholipase A2 (PLA2) that is secreted into the airways and is increased in asthma in association with the severity of AHR. The PLA2s are a group of enzymes that catalyze the rate-limiting step in the formation of eicosanoids such as leukotrienes (LTs) and prostaglandins (PGs), and novel members of this enzyme family are secreted (sPLA2s).
Although 12 members of this sPLA2 family have been described in mammals, prior work demonstrates that the majority of the relevant sPLA2 activity in the airways is attributable to a specific enzyme sPLA2 group 10 (sPLA2-X) and that the levels of this enzyme in the airways are about 2-3 times higher in asthma and correlate with the degree of AHR.
Professors Teal Hallstrand and William Altemeier (Pulmonary, Critical Care and Sleep Medicine) have identified a specific secreted phospholipase A2 (group 10, sPLA2-X) that is elevated in the airways in individuals with asthma and plays a key role in airway dysfunction. They have received funding from the National Heart Lung and Blood Institute to determine precisely how sPLA2-X functions to regulate innate and adaptive immune responses in asthma so that it can be effectively targeted therapeutically.
“We discovered secreted PLA2 group X during a candidate screen for regulators of the increased production of lipid mediators in asthma,” said Hallstrand. “We found that this specific PLA2 is 2-3 times higher in the airways of individuals with asthma, and related to airway dysfunction and severity. Deletion of the gene for this enzyme in mouse models shows that it plays key roles in both the initiation and maintenance of inflammation.”