Effect of exogenous prostaglandin E2 and actinomycin D on plasma leakage induced by neutrophil-activating peptide-1/interleukin-8.
Neutrophil accumulation and plasma leakage were measured in rabbit skin at sites stimulated with recombinant human neutrophil activating peptide-1/interleukin-8 (NAP-1/IL-8). Neutrophil accumulation occurred at doses equal to or greater than 10(-11) moles NAP-1/IL-8 per site. Co-injection of prostaglandin E2 (PGE2) extended the threshold of inflammatory activity of NAP-1/IL-8 to less than 10(-13) moles/site and caused approximately three-fold increases in neutrophil accumulation and ten-fold increases in plasma leakage at the higher doses of NAP-1/IL-8 examined. Plasma leakage declined more rapidly than did neutrophil accumulation as lesions aged. It was postulated that an endothelial response may be initiated to limit plasma leakage during ongoing neutrophil emigration at sites stimulated with NAP-1/IL-8. The induction of vasodilatation by injection of PGE2 masked the decline of plasma leakage with time in lesions up to 120 min old. Co-injection of the RNA synthesis inhibitor, actinomycin D, failed to abrogate the decline of plasma leakage with time, suggesting that de novo protein synthetic events such as production of the vasoconstrictor peptide, endothelin, are unlikely to contribute to the mechanism that restricts plasma leakage in older lesions. Although plasma leakage induced by NAP-1/IL-8 is dependent on the emigration of neutrophils, the results indicate that a mechanism, independent of de novo protein synthesis, restricts the rate of plasma leakage per neutrophil as lesions age.
Colditz
I G
IG
CSIRO Division of Animal Health, Armidale, NSW, Australia.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D016209:Interleukin-8 / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D010949:Plasma / Q000187:drug effects*; D011817:Rabbits; D011994:Recombinant Proteins; D012867:Skin / Q000098:blood supply; D013997:Time Factors
D016209:Interleukin-8; D011994:Recombinant Proteins; D003609:Dactinomycin; D006632:Histamine; D015232:Dinoprostone; D001920:Bradykinin