Coupling of neutrophil apoptosis to recognition by macrophages: coordinated acceleration by protein synthesis inhibitors.
Onset of apoptosis in many cell types, including the neutrophil granulocyte, leads to recognition and ingestion by macrophages, a key regulatory step in clearance of inflammatory cells from inflamed sites. These studies examined the requirement for protein synthesis in neutrophil apoptosis and in the recognition of apoptotic neutrophils by monocyte-derived macrophages. Treatment with cycloheximide or actinomycin D produced a time- and concentration-dependent acceleration of apoptosis in populations of neutrophils purified from human peripheral blood. Both compounds caused significant promotion of apoptosis after 8 h (apoptosis was 7.7 +/- 2.9%, mean +/- SEM, in control populations, 57.5 +/- 4.9% in cycloheximide-treated, and 73.4 +/- 5.5% in actinomycin D-treated populations, n = 4, P < 0.001), which was associated with loss of neutrophil functional ability (assessed by shape change on N-formyl-methionyl-leucyl-phenylalanine stimulation) and increased macrophage recognition and ingestion of neutrophil populations with accelerated apoptosis. These results support the existence of survival proteins, which act as intracellular suppressors of programmed cell death. However, protein synthesis was not required for the recognition process because macrophage recognition was increased pari passu with the morphology of apoptosis.
Whyte
M K
MK
Department of Medicine, University Hospital, Nottingham, United Kingdom.
Savill
J
J
Meagher
L C
LC
Lee
A
A
Haslett
C
C
D017209:Apoptosis / Q000187:drug effects; D048429:Cell Size; D002470:Cell Survival; D016922:Cellular Senescence; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology*; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D003513:Cycloheximide