COUPLING OF NEUTROPHIL APOPTOSIS TO RECOGNITION BY MACROPHAGES - COORDINATED ACCELERATION BY PROTEIN-SYNTHESIS INHIBITORS

Onset of apoptosis in many cell types, including the neutrophil granul ocyte, leads to recognition and ingestion by macrophages, a key regula tory step in clearance of inflammatory cells from inflamed sites. Thes e 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 pr oduced a time- and concentration-dependent acceleration of apoptosis i n populations of neutrophils purified from human peripheral blood. Bot h compounds caused significant promotion of apoptosis after 8 h (apopt osis 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-trea ted populations, n = 4, P < 0.001), which was associated with loss of neutrophil functional ability (assessed by shape change on N-formyl-me thionyl-leucyl-phenylalanine stimulation) and increased macrophage rec ognition and ingestion of neutrophil populations with accelerated apop tosis, These results support the existence of survival proteins, which act as intracellular suppressors of programmed cell death, However, p rotein synthesis was not required for the recognition process because macrophage recognition was increased pari passu with the morphology of apoptosis.