Multiple Roles of Phospholipase A2 during Lung Infection and Inflammation
Bryan P. Hurley and Beth A. McCormick

Infection and Immunity, June 2008, p. 2259-2272, Vol. 76, No. 6

There exists a substantial diversity of PLA2 enzymes present in the airway that are capable of influencing the inflammatory process during the course of lung diseases, such as ARDS, pneumonia, CF, asthma, and COPD (Fig. 3). Many types of host cells, as well as bacterial invaders, are capable of synthesizing PLA2 enzymes that, as a whole, represent a large family of enzymes with a broad range of structure and specificity. The functional consequences of each distinct PLA2 operating in the lung are quite heterogeneous and can be beneficial or damaging to the host, depending on the context. Certain PLA2s are bactericidal and serve to eradicate invading pathogens, while others are immunomodulatory and can neutralize potent soluble bioactive lipids, such as PAF. Several PLA2 enzymes participate in various aspects of surfactant production and degradation which must be tightly orchestrated or severe lung pathology ensues. PLA2 involvement in eicosanoid synthesis and modulation of cell signaling and cytokine production may have beneficial or detrimental consequences, depending on the particular eicosanoid generated, as well as the context, location, and stage of disease in which the eicosanoid or modulated cytokine is produced. It is also important to reiterate that overlapping functions exist among the various PLA2 enzymes, making investigation of the roles of individual PLA2 enzymes challenging. Targeting PLA2s as a means to treat lung disease holds tremendous promise and represents a worthy pursuit; however, a more-thorough appreciation of the considerable diversity of lung-associated PLA2 enzymes, their specificity, and their cell sources, as well as their discrete role in various lung diseases, will be necessary to ensure the efficacy, as well as the safety, of any PLA2-based therapeutic.

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