title: Group V secretory phospholipase A2 is involved in macrophage activation and is sufficient for macrophage effector functions in allergic pulmonary inflammation.
abstract: We reported that Pla2g5-null mice lacking group V secretory phospholipase A2 (gV-sPLA2) showed reduced eosinophilic pulmonary inflammation and Th2 cytokine generation when challenged with an extract from house dust mite Dermatophagoides farinae, compared with wild-type (WT) controls. Adoptive transfer studies suggested that gV-sPLA2 in dendritic cells was necessary for sensitization of Pla2g5-null mice, but was not sufficient to induce the effector phase of pulmonary inflammation. In this study, we demonstrate that gV-sPLA2 is inducibly expressed in mouse and human macrophages (M) activated by IL-4 and is required for the acquisition of M effector functions that facilitate the effector phase of pulmonary inflammation. We demonstrate that gV-sPLA2 expression in M is sufficient for the development of pulmonary inflammation, even when inflammation is induced by intrapulmonary administration of IL-4. The concentrations of CCL22/CCL17 and effector T cell recruitment are severely impaired in Pla2g5-null mice. Intratracheal transfers of enriched CD68(+) cells isolated from the lungs of D. farinae-challenged WT donor mice induce eosinophilia, chemokine production, and recruitment of T cells into the lungs of Pla2g5-null recipients previously sensitized by WT D. farinae-loaded dendritic cells. Our studies identified a unique function of gV-sPLA2 in activation of M and in their capacity to recruit T cells to amplify the effector phase of pulmonary inflammation.
authors: Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors: Shin
authors: S
authors: Ohta
authors: Mitsuru
authors: M
authors: Imamura
authors: Wei
authors: W
authors: Xing
authors: Joshua A
authors: JA
authors: Boyce
authors: Barbara
authors: B
authors: Balestrieri
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D054505:Group V Phospholipases A2 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D054505:Group V Phospholipases A2
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