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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Apoptosis, DNA Fragmentation, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Lipopolysaccharides, Mitogen-Activated Protein Kinases, Neutrophils, Ultraviolet Rays.
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Does granulocyte-macrophage colony-stimulating factor rescue human polymorphonuclear leukocytes from ultraviolet irradiation-accelerated apoptosis? Context: Bacterial lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) delay PMN apoptosis during in vitro culture. The present study was undertaken to determine if LPS and GM-CSF can rescue UV-irradiated PMN from undergoing apoptosis and to determine the role of extracellular signal-regulated kinase (ERK) in this process. PMN were preincubated with LPS (20 ng/ml) and GM-CSF (100 units/ml) for 60 min before being UV-irradiated for 15 min. Additional PMN were UV-irradiated for 15 min and then treated with LPS and GM-CSF. To determine the role of ERK in protection or rescue of PMN from apoptosis, PMN were preincubated with PD098059 for 30 min. Morphologic features of apoptosis were determined 4 h after UV irradiation. DNA laddering was confirmed by agarose gel electrophoresis. LPS and GM-CSF pretreatment significantly protected PMN from UV-accelerated apoptosis, although GM-CSF was more effective than LPS. Only GM-CSF rescued PMN that had already been exposed to UV irradiation from undergoing apoptosis. Time response experiments demonstrated that GM-CSF rescued a significant percentage of PMN when added up to 90 min after UV irradiation. Inhibition of ERK with PD098059 abrogated the protective effect of LPS and GM-CSF and blocked rescue of PMN from apoptosis by GM-CSF.
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LPS and GM-CSF protect PMN, whereas only GM-CSF can rescue PMN from UV-accelerated apoptosis. The ERK-signaling pathway plays an important role in the protection and/or rescue of PMN from UV-accelerated apoptosis, but appears to be a proximal event in this process. This study provides further insight into factors that regulate PMN apoptosis and provides a novel approach for investigating signal transduction pathways involved in PMN apoptosis. Final Decision: yes