Secreted phospholipases A2: A proinflammatory connection between macrophages and mast cells in the human lung

Secretory phospholipases A2 (sPLA2) are an emerging class of mediators of inflammation. These enzymes accumulate in plasma and other biological fluids of patients with inflammatory, autoimmune and allergic diseases. sPLA2s are secreted at low levels in the normal airways and tend to increase during inflammatory lung diseases (e.g. bronchial asthma, chronic obstructive pulmonary disease, interstitial lung fibrosis, and sarcoidosis) as the result of plasma extravasation and/or local production. Such immune resident cells as macrophages and mast cells can be a source of sPLA2s in the lung. However, these cells are also targets for sPLA2s that sustain the activation programs of macrophages and mast cells with mechanism related to their enzymatic activity as well as to their capacity to interact with surface molecules (e.g., heparan sulfate proteoglycans, M-type receptor, mannose receptor). Recent evidence suggests that mast cells are a better source of extracellular sPLA2s than macrophages. On the other hand, macrophages appear to be a preferential target for sPLA2s. Anatomical association between macrophages and mast cells in the airways suggest that sPLA2s released by mast cells may activate in a paracrine fashion several macrophage functions relevant to the modulation of lung inflammation. Thus, sPLA2s may play a major role in inflammatory lung diseases by acting as a proinflammatory connection between macrophages and mast cells.