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: Shin Ohta, Mitsuru Imamura, Wei Xing, Joshua A Boyce, Barbara Balestrieri
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 190 Issue 12 Pg. 5927-38 (Jun 15 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 23650617 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Group V Phospholipases A2

Topics

• Animals
• Fluorescent Antibody Technique
• Group V Phospholipases A2 (immunology, metabolism)
• Humans
• Hypersensitivity (immunology, metabolism)
• Immunohistochemistry
• Lymphocyte Activation (immunology)
• Macrophage Activation (immunology)
• Macrophages (immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pneumonia (immunology, metabolism)
• T-Lymphocytes (immunology, metabolism)