Group V secretory phospholipase A2 modulates phagosome maturation and regulates the innate immune response against Candida albicans

B Balestrieri, A Maekawa, W Xing, MH Gelb… - The Journal of …, 2009 - journals.aai.org
B Balestrieri, A Maekawa, W Xing, MH Gelb, HR Katz, JP Arm
The Journal of Immunology, 2009journals.aai.org
Abstract Phospholipase A 2 (PLA 2) hydrolyzes the sn-2 position of cell membrane
phospholipids to release fatty acids and lysophospholipids. We have previously reported
that group V secretory PLA 2 (sPLA 2) 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 sPLA 2, phagosome maturation was reduced 50–60% at …
Abstract
Phospholipase A 2 (PLA 2) hydrolyzes the sn-2 position of cell membrane phospholipids to release fatty acids and lysophospholipids. We have previously reported that group V secretory PLA 2 (sPLA 2) 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 sPLA 2, phagosome maturation was reduced 50–60% at early time points while the binding of zymosan was unimpaired. The ability of group V sPLA 2 to regulate phagocytosis extended to phagocytosis of IgG-and complement-opsonized sheep RBC. Moreover, macrophages lacking group V sPLA 2 had delays in phagocytosis, phagosome maturation, and killing of Candida albicans. Cytokine production and eicosanoid generation were not impaired by the lack of group V sPLA 2. Furthermore, in a model of systemic candidiasis, mice lacking group V sPLA 2 had an increased fungal burden in the kidney, liver, and spleen at day 7 postinfection and increased mortality. Thus, group V sPLA 2 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.
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