Neutrophil infiltration into the ischaemic/reperfused rabbit isolated myocardium: effect of PF-5901 and cycloheximide.
The Langendorff-perfused rabbit heart preparation has been used to study the interaction of isolated rabbit neutrophils with regionally ischaemic myocardium. Short durations of regional ischaemia (10-60 min) and subsequent reperfusion (30 min) of the hearts with neutrophils resulted in a significant time-dependent accumulation of neutrophils (as assessed by myeloperoxidase activity) in the area at risk. Pre-activation of neutrophils with zymosan-activated serum prior to their infusion into the myocardium potentiated neutrophil accumulation in the area at risk. Pretreatment of the myocardium with a lipoxygenase inhibitor, PF-5901 (10 microM), or a de novo protein synthesis inhibitor, cycloheximide (10 microM), significantly reduced the accumulation of neutrophils in the ischaemic/reperfused myocardium. In contrast, pretreatment of neutrophils with cycloheximide (10 microM, for 15 min) prior to their infusion had no significant effect on neutrophil accumulation in the area at risk. The cyclooxygenase inhibitor, indomethacin (10 microM), had no effect on neutrophil accumulation in the area at risk following ischaemia and reperfusion. These results suggest the involvement of de novo protein synthesis and the lipoxygenase products in the infiltration of neutrophils following ischaemia and reperfusion in vitro.
Lad
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Department of Biology, Roche Products Ltd., Welwyn Garden City, UK.
Williams
T J
TJ
Booth
R F
RF
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D015054:Zymosan
D016859:Lipoxygenase Inhibitors; D011804:Quinolines; C049740:alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; D015054:Zymosan; D003513:Cycloheximide; D009195:Peroxidase; D007213:Indomethacin