Group V Secretory Phospholipase A2 Modulates Phagosome Maturation and Regulates the Innate Immune Response against

Phospholipase A2 (PLA2) hydrolyzes the sn-2 position of cell membrane phospholipids to release fatty acids and lysophospholipids. We have previously reported that group V secretory PLA2 (sPLA2) translocates from the Golgi and recycling endosomes of mouse peritoneal macrophages to newly formed phagosomes and regulates the phagocytosis of zymosan, suggesting a role in innate immunity. Here we report that in macrophages lacking group V sPLA2, phagosome maturation was reduced 50–60 % at early time points while the binding of zymosan was unimpaired. The ability of group V sPLA2 to regulate phagocytosis extended to phago-cytosis of IgG- and complement-opsonized sheep RBC. Moreover, macrophages lacking group V sPLA2 had delays in phagocy-tosis, phagosome maturation, and killing of Candida albicans. Cytokine production and eicosanoid generation were not impaired by the lack of group V sPLA2. Furthermore, in a model of systemic candidiasis, mice lacking group V sPLA2 had an increased fungal burden in the kidney, liver, and spleen at day 7 postinfection and increased mortality. Thus, group V sPLA2 regulates phagocytosis through major phagocytic receptors and contributes to the innate immune response against C. albicans by regulating phagocytosis and killing through a mechanism that is likely dependent on phagolysosome fusion. The Journal of Immunology, 2009, 182: 4891–4898. P hagocytosis, the process whereby phagocytic cells inter-nalize large particles, is a key component of innate immu-nity (1). The mechanisms of phagocytosis depend on sev-eral variables, including the type of phagocytic cell, the nature of the stimulus, the number and types of receptors involved, and th