Chemotactic 5-Oxo-Eicosatetraenoic Acids Induce Oxygen Radical Production, Ca2+-Mobilization, and Actin Reorganization in Human Eosinophils via a Pertussis Toxin-Sensitive G-Protein

The arachidonic acid metabolites 5-oxo-[6E,8Z, 11Z,14Z]-eicosatetraenoic acid (5oETE) and 5-oxo-15-hydroxy-[6E,8Z,11Z,13E]-eicosatetraenoic acid (5oHETE) are potent eosinophil chemotaxins. Here, the activation profile of 5-oxo-eicosanoids in eosinophils was further characterized and compared to othe...

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Bibliographic Details
Published in:Journal of investigative dermatology 1997-01, Vol.108 (1), p.108-112
Main Authors: Czech, Wolfgang, Barbisch, Michael, Tenscher, Kirsten, Schöpf, Erwin, Schröder, Jens-Michael, Norgauer, Johannes
Format: Article
Language:English
Subjects:
Actins - chemistry
Arachidonic Acids - pharmacology
Biological and medical sciences
Calcium - metabolism
Chemotactic Factors - pharmacology
Dermatology
Dyskeratosis
Eosinophils - metabolism
GTP-Binding Proteins - physiology
Humans
Medical sciences
Pertussis Toxin
Reactive Oxygen Species - metabolism
Respiratory Burst - drug effects
Virulence Factors, Bordetella - pharmacology
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Summary:The arachidonic acid metabolites 5-oxo-[6E,8Z, 11Z,14Z]-eicosatetraenoic acid (5oETE) and 5-oxo-15-hydroxy-[6E,8Z,11Z,13E]-eicosatetraenoic acid (5oHETE) are potent eosinophil chemotaxins. Here, the activation profile of 5-oxo-eicosanoids in eosinophils was further characterized and compared to other eosinophil activators such as complement fragment C5a (C5a), platelet-activating factor (PAF), interleukin-5 (IL-5)and phorbol ester (PMA). Flow cytometric studies revealed a rapid and transient actin polymerization upon stimulation by both 5-oxo-eicosanoids. Desensitization studies using actin polymerization as the parameter indicated cross-desensitization between the two 5-oxo-eicosanoids but revealed no interference with the response to other chemotaxins. Fluorescence measurements with Fura-2-labeled eosinophils in the presence of EGTA indicated Ca2+-mobilization from intracellular stores by 5oETE and 5oHETE. Both 5-oxo-eicosanoids stimulated the production of reactive oxygen metabolites as demonstrated by lucigenin-dependent chemiluminescence, superoxide dismutase-inhibitable cytochrome C reduction and flow cytometric dihydro-rhodamine-123 analysis. At optimal concentrations the changes induced by 5-oxo-eicosanoids were comparable to those obtained by C5a and PAF, whereas IL-5 and PMA induced only a restricted pattern of cell responses. Cell responses elicited by 5-oxo-eicosanoids were inhibited by pertussis toxin, indicating coupling of the putative 5-oxo-eicosanoid-receptor to G-proteins. These results indicate that 5-oxo-eicosanoids are stong activators of eosinophils with comparable biologic activity to the eosinophil chemotaxins C5a and PAR These findings point to a role of 5-oxo-eicosanoids in the pathogenesis of eosinophilic inflammation as chemotaxins as well as activators of pro-inflammatory activities.
ISSN:0022-202X
1523-1747
DOI:10.1111/1523-1747.ep12285653