Eosinophil lipid bodies: specific, inducible intracellular sites for enhanced eicosanoid formation.
The specific intracellular sites at which enzymes act to generate arachidonate-derived eicosanoid mediators of inflammation are uncertain. We evaluated the formation and function of cytoplasmic lipid bodies. Lipid body formation in eosinophils was a rapidly (<1 h) inducible response which was platelet-activating factor (PAF) receptor-mediated, involved signaling through protein kinase C, and required new protein synthesis. In intact and enucleated eosinophils, the PAF-induced increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. All principal eosinophil eicosanoid-forming enzymes, 5-lipoxygenase, leukotriene C4 synthase, and cyclooxygenase, were immunolocalized to native as well as newly induced lipid bodies in intact and enucleated eosinophils. Thus, lipid bodies are structurally distinct, inducible, nonnuclear sites for enhanced synthesis of paracrine eicosanoid mediators of inflammation.
Bozza
P T
PT
Harvard Thorndike Laboratory and Charles A. Dana Research Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Yu
W
W
Penrose
J F
JF
Morgan
E S
ES
Dvorak
A M
AM
Weller
P F
PF
D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction
D015777:Eicosanoids; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D010972:Platelet Activating Factor; D011500:Protein Synthesis Inhibitors; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D005982:Glutathione Transferase; D011493:Protein Kinase C; C041116:leukotriene-C4 synthase