The role of mast cell-derived secreted phospholipases A2 in respiratory allergy

Secreted phospholipases A2 (sPLA2s) are molecules released in plasma and biological fluids of patients with systemic inflammatory, autoimmune and allergic diseases. These molecules exert proinflammatory effects by either enzymatic-mechanisms or through binding to surface molecules expressed on inflammatory cells. sPLA2s are released at low levels in the normal airways and tend to increase during respiratory allergies (e.g., rhinitis and bronchial asthma) as the result of local secretion. Several sPLA2 isoforms are expressed in the human lung and some of them (e.g., group IIA and group X) are released in the airways of patients with rhinitis or asthma. Mast cells play a major role in the pathogenesis of respiratory allergies and other chronic inflammatory lung diseases. Recent evidence indicates that mast cells purified from human lung express most of the sPLA2 isoforms so far described. IgE-mediated activation of these cells induce the release of sPLA2s suggesting that mast cells are a main source of extracellular sPLA2s during allergic reactions. Once released, sPLA2s may contribute to the generation of eicosanoids (e.g., PGD2 and LTC4) and to the release of preformed mediators (e.g., histamine) by an autocrine loop involving the interaction of sPLA2s with surface molecules such as heparan sulphate proteoglycans or the M-type receptor. Thus, mast cell-derived sPLA2s may play an important role in the initiation and amplification of the inflammatory reactions in patients with allergic rhinitis and bronchial asthma.