Impact of arachidonic versus eicosapentaenoic acid on exotonin-induced lung vascular leakage: relation to 4-series versus 5-series leukotriene generation
| Autor: | F. Grimminger, Werner Seeger, Dieter Walmrath, K Mayer, H. Wahn, Ladislau Kiss |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Leukotrienes Vascular permeability Inflammation Pharmacology Critical Care and Intensive Care Medicine medicine.disease_cause Capillary Permeability chemistry.chemical_compound Hemolysin Proteins Bacterial Proteins Medicine Animals Lung Leukotriene Arachidonic Acid Dose-Response Relationship Drug business.industry Toxin Escherichia coli Proteins Hemodynamics respiratory system Eicosapentaenoic acid chemistry Biochemistry Eicosapentaenoic Acid lipids (amino acids peptides and proteins) Arachidonic acid Female Rabbits medicine.symptom business Vasoconstriction Exotoxin |
| Zdroj: | American journal of respiratory and critical care medicine. 155(2) |
| ISSN: | 1073-449X |
| Popis: | Escherichia coli hemolysin (HlyA) is a proteinaceous pore-forming exotoxin that is implicated as a significant pathogenicity factor in extraintestinal E. coli infections including sepsis. In perfused rabbit lungs, subcytolytic concentrations of the toxin evoke thromboxane-mediated vasoconstriction and prostanoid-independent protracted vascular permeability increase (11). In the present study, the influence of submicromolar concentrations of free arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the HlyA-induced leakage response was investigated. HlyA at concentration from 0.02 to 0.06 hemolytic units/ml provoked a dose-dependent, severalfold increase in the capillary filtration coefficient (Kfc), accompanied by the release of leukotriene(LT)B4, LTC4, and LTE4 into the recirculating buffer fluid. Simultaneous application of 100 nmol/L AA markedly augmented the HlyA-elicited leakage response, concomitant with an amplification of LTB4 release and a change in the kinetics of cysteinyl-LT generation. In contrast, 50 to 200 nmol/L EPA suppressed in a dose-dependent manner the HlyA-induced increase in Kfc values. This was accompanied by a blockage of 4-series LT generation and a dose-dependent appearance of LTB5, LTC5, and LTE5. In addition, EPA fully antagonized the AA-induced amplification of the HlyA-provoked Kfc increase, again accompanied by a shift from 4-series to 5-series LT generation. We conclude that the vascular leakage provoked by HlyA in rabbit lungs is differentially influenced by free AA versus free EPA, related to the generation of 4- versus 5-series leukotrienes. The composition of lipid emulsions used for parenteral nutrition may thus influence inflammatory capillary leakage. |
| Databáze: | OpenAIRE |
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