The cellular biology of eosinophil eicosanoid formation and function

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Presentation transcript:

The cellular biology of eosinophil eicosanoid formation and function Christianne Bandeira-Melo, PhDa, b, Patricia T. Bozza, MD, PhDb, Peter F. Weller, MDa Journal of Allergy and Clinical Immunology Volume 109, Issue 3, Pages 393-400 (March 2002) DOI: 10.1067/mai.2002.121529 Copyright © 2002 Mosby, Inc. Terms and Conditions

Fig. 1 Schematic summary of studies evaluating 5-LO localization within human eosinophils. Intracellular sites of immunolocalized 5-LO protein within eosinophils, highlighted in red, changed from primarily cytosolic to different compartments in response to varied priming agents and subsequent activation by varied concentrations (range, 0.1-10 μmol/L) of calcium ionophore (A23187). LTC4 released from eosinophils was detected by means of ELISA. n.d. , Not determined. Journal of Allergy and Clinical Immunology 2002 109, 393-400DOI: (10.1067/mai.2002.121529) Copyright © 2002 Mosby, Inc. Terms and Conditions

Fig. 2 Immunogold localization of 5-LO within lipid bodies of unstimulated eosinophils from a donor with hypereosinophilic syndrome shows gold labeling, indicating 5-LO in lipid bodies (A and C ), which was absent from control 5-LO-absorbed anti-5-LO antisera (B ) or nonimmune sera (D ). Lipid bodies are surrounded by a monolayer of phospholipids and contain a nonhomogeneously dense organization with numerous small compartments and an internal honeycomb structure. In C , several gold particles reside in the perinuclear cistern (arrow) . In A , cytoplasmic tubules and vesicles of smooth endoplasmic reticulum adjacent to the lipid body also have gold particles associated with them (arrows) . Images reproduced with permission from J Exp Med . © Copyright by The Rockefeller University Press.44 Journal of Allergy and Clinical Immunology 2002 109, 393-400DOI: (10.1067/mai.2002.121529) Copyright © 2002 Mosby, Inc. Terms and Conditions

Fig. 3 Cellular-signaling pathways that elicit the formation of new lipid bodies within human eosinophils. Various physiologic stimuli acting on their specific receptors, including exogenous PAF, both IL-5 and IgG immune complexes acting by means of endogenous PAF formation, and the CCR3 agonists eotaxin and RANTES are able to induce lipid body formation by activating distinct downstream kinases. PTX , Pertussis toxin; ERK , extracellular signal-regulated kinase. Scissors symbol denotes inhibition. Journal of Allergy and Clinical Immunology 2002 109, 393-400DOI: (10.1067/mai.2002.121529) Copyright © 2002 Mosby, Inc. Terms and Conditions

Fig. 4 Cytoplasmic lipid bodies and perinuclear membranes as sites of LTC4 synthesis in eosinophils. Intracellular immunofluorescent localization of newly formed LTC4 (green staining) is present at cytoplasmic lipid bodies in eotaxin-primed eosinophils (top) and at both lipid bodies and perinuclear membranes in eotaxin-primed and A23187-challenged eosinophils (bottom) . Eosinophil plasma membranes and perinuclear membranes have been outlined with dotted white and blue lines, respectively, to facilitate intracellular localization. Newly formed LTC4 was cross-linked to adjacent proteins with a water-soluble carbodiimide and detected with a green fluorochrome-conjugated anti-cysLT mAb, as detailed elsewhere.13 Journal of Allergy and Clinical Immunology 2002 109, 393-400DOI: (10.1067/mai.2002.121529) Copyright © 2002 Mosby, Inc. Terms and Conditions