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.