Functional eicosanoid test and typing (FET) of peripheral blood cells in eicosanoids related diseases.
Monitoring of eicosanoid synthesis in peripheral blood cells has significant potential for improving the diagnosis and therapy of many human diseases. The quantitative relation between concentrations of prostaglandins and leukotrienes is central to the physiologic function of the eicosanoid network. Here we show that this regulation, which we call the functional eicosanoid typing (FET), fluctuates dynamically in individual living blood cells from patients, thereby limiting the accuracy with which concentration circuits of eicosanoids can transfer metabolic information. Using living cells in functional cell testing, we characterised the eicosanoid pattern score (EPS). A novel technique based on binomial errors on lipid mediator partitioning enabled calibration of in vivo biochemical parameters in molecular units. We found that eicosanoid production rates fluctuate over a time scale of about twenty minutes, while intrinsic noise decays rapidly. Thus, biochemical eicosanoid parameters, noise, and slowly varying cellular states together determine the effective FET. These results can form a basis for quantitative modelling of natural eicosanoid circuits in diagnosis of eicosanoid related diseases and design of synthetic ones for the prediction other diseases.
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Medizinische Klinik III mit Poliklinik, Abteilung für Allergologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstr. 29, D-91054 Erlangen, Germany. schaefer.dk@web.de
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D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis / Q000503:physiopathology*; D001773:Blood Cells / Q000378:metabolism; D002138:Calibration; D016022:Case-Control Studies; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013276:Stomach Ulcer / Q000175:diagnosis / Q000503:physiopathology*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015289:Leukotrienes; D015232:Dinoprostone