Protein synthesis dependent and independent mechanisms of neutrophil emigration. Different mechanisms of inflammation in rabbits induced by interleukin-1, tumor necrosis factor alpha or endotoxin versus leukocyte chemoattractants.
Inflammation constitutes the body's principal mode of defense against infection and other harmful agents. Neutrophil leukocytes are the primary effector cells in this process. The role of protein synthesis in neutrophil emigration into acute inflammatory lesions was examined. Local intradermal injections of actinomycin D, cycloheximide or puromycin could inhibit in a dose- and time-dependent manner neutrophil emigration induced by interleukin-1, tumor necrosis factor alpha or endotoxin, but not by the leukocyte chemoattractants C5a des arg (zymosan-activated plasma), n-formyl-methionyl-leucyl-phenylalanine or leukotriene B4. Maximal inhibition, measured at the time of peak emigration, was greater than 90%. The onset of neutrophil emigration induced by the cytokines or by endotoxin was delayed by 30 to 60 minutes in comparison to the leukocyte chemoattractants. These results demonstrate at least two mechanisms of neutrophil emigration: one with a slower onset and dependence on local RNA transcription and translation and the other rapid in onset and independent of protein synthesis.
Cybulsky
M I
MI
Department of Pathology, University of Toronto, Ontario, Canada.
McComb
D J
DJ
Movat
H Z
HZ
D000818:Animals; D002630:Chemotactic Factors; D003182:Complement C5 / Q000031:analogs & derivatives / Q000378:metabolism; D015937:Complement C5a, des-Arginine; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004731:Endotoxins / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology*; D007700:Kinetics; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage; D011506:Proteins / Q000276:immunology; D011691:Puromycin / Q000494:pharmacology; D012313:RNA / Q000235:genetics; D011817:Rabbits; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D002630:Chemotactic Factors; D003182:Complement C5; D015937:Complement C5a, des-Arginine; D004731:Endotoxins; D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D007975:Leukotriene B4; D011691:Puromycin; D012313:RNA; D003513:Cycloheximide