Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Macrophage secretory phospholipase A2 group X enhances anti-inflammatory responses, promotes lipid accumulation, and contributes to aberrant lung pathology. 1851 24

Anagrelide, a phospholipase A2 inhibitor, is widely used in the management of essential thrombocythemia. To date, anagrelide has only rarely been reported to be associated with the development of drug-induced interstitial pneumonitis. We herein report two cases of anagrelide-associated interstitial pneumonitis. The patients were a 67-year-old woman and a 75-year-old man, both with essential thrombocythemia. Both cases developed interstitial pneumonitis at 8 weeks after administration of anagrelide. Because anagrelide-induced interstitial pneumonitis was suspected from CT scan and bronchoalveolar lavage fluid findings, anagrelide-therapy was discontinued and corticosteroid administration was initiated. Anagrelide withdrawal and corticosteroid administration resulted in marked symptom amelioration. A lymphocyte stimulation test using anagrelide was positive in both cases. As interstitial pneumonitis is a rare adverse event during anagrelide-therapy administration, physicians must be vigilant in identifying drug-induced interstitial pneumonitis in patients treated with anagrelide because early detection can decrease the severity and prevent mortality.
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PMID:Drug-induced interstitial pneumonitis in essential thrombocythemia treated with anagrelide. 2832 Oct 88