Macrophage secretory phospholipase A2 group X enhances anti-inflammatory responses, promotes lipid accumulation, and contributes to aberrant lung pathology.

Curfs, D; Ghesquiere, SA; Vergouwe, M; van der Made, I; Gijbels, M; Greaves, D; Verbeek, J; Hofker, M; Winther, d

Journal article

Macrophage secretory phospholipase A2 group X enhances anti-inflammatory responses, promotes lipid accumulation, and contributes to aberrant lung pathology.

Abstract:: Secreted phospholipase A2 group X (sPLA(2)-X) is one of the most potent enzymes of the phospholipase A(2) lipolytic enzyme superfamily. Its high catalytic activity toward phosphatidylcholine (PC), the major phospholipid of cell membranes and low-density lipoproteins (LDL), has implicated sPLA(2)-X in chronic inflammatory conditions such as atherogenesis. We studied the role of sPLA(2)-X enzyme activity in vitro and in vivo, by generating sPLA(2)-X-overexpressing macrophages and transgenic macrophage-specific sPLA(2)-X mice. Our results show that sPLA(2)-X expression inhibits macrophage activation and inflammatory responses upon stimulation, characterized by reduced cell adhesion and nitric oxide production, a decrease in tumor necrosis factor (TNF), and an increase in interleukin (IL)-10. These effects were mediated by an increase in IL-6, and enhanced production of prostaglandin E(2) (PGE(2)) and 15-deoxy-Delta12,14-prostaglandin J(2) (PGJ(2)). Moreover, we found that overexpression of active sPLA(2)-X in macrophages strongly increases foam cell formation upon incubation with native LDL but also oxidized LDL (oxLDL), which is mediated by enhanced expression of scavenger receptor CD36. Transgenic sPLA(2)-X mice died neonatally because of severe lung pathology characterized by interstitial pneumonia with massive granulocyte and surfactant-laden macrophage infiltration. We conclude that overexpression of the active sPLA(2)-X enzyme results in enhanced foam cell formation but reduced activation and inflammatory responses in macrophages in vitro. Interestingly, enhanced sPLA(2)-X activity in macrophages in vivo leads to fatal pulmonary defects, suggesting a crucial role for sPLA(2)-X in inflammatory lung disease.

Publication status:: Published

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APA Style

Curfs, D., Ghesquiere, S. A., Vergouwe, M., van der Made, I., Gijbels, M., Greaves, D., Verbeek, J., Hofker, M., & Winther, d. (2008). Macrophage secretory phospholipase A2 group X enhances anti-inflammatory responses, promotes lipid accumulation, and contributes to aberrant lung pathology. Journal of Biological Chemistry, 283(31), 21640–21648.

MLA Style

Curfs, D., et al. “Macrophage Secretory Phospholipase A2 Group X Enhances Anti-Inflammatory Responses, Promotes Lipid Accumulation, and Contributes to Aberrant Lung Pathology.” Journal of Biological Chemistry, vol. 283, no. 31, 2008, pp. 21640–48.

Chicago Style

Curfs, D, SA Ghesquiere, M Vergouwe, I van der Made, M Gijbels, D Greaves, J Verbeek, M Hofker, and d Winther. 2008. “Macrophage Secretory Phospholipase A2 Group X Enhances Anti-Inflammatory Responses, Promotes Lipid Accumulation, and Contributes to Aberrant Lung Pathology.” Journal of Biological Chemistry 283 (31): 21640–48.
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