Granulocyte-macrophage, colony-stimulating factor ensures macrophage survival and generation of the superoxide anion: A study using a monocytic-differentiated HL60 subline

Citation
M. Ujihara et al., Granulocyte-macrophage, colony-stimulating factor ensures macrophage survival and generation of the superoxide anion: A study using a monocytic-differentiated HL60 subline, FREE RAD B, 31(11), 2001, pp. 1396-1404
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN journal
0891-5849 → ACNP
Volume
31
Issue
11
Year of publication
2001
Pages
1396 - 1404
Database
ISI
SICI code
0891-5849(200112)31:11<1396:GCFEMS>2.0.ZU;2-#
Abstract
A large number of constituents, such as growth factors, cytokines, and vaso regulatory molecules, contribute a network of cellular interactions to athe rosclerotic lesions, and current evidence suggests that granulocyte-macroph age colony-stimulating factor (GM-CSF) is one of these constituents. We con ducted this study to determine whether GM-CSF has an effect on the fate and function of macrophages. We examined the effect of GM-CSF on macrophages i n vitro with a highly inducible HL60 subclone (HL60/DU-1) that we recently established. HL60 cells have been reported to preserve functional GM-CSF re ceptors, but a GM-CSF allele was rearranged and partially deleted. HL60/DU- 1 cells were devoid of GM-CSF immunoreactivity and of autocrine stimulation of GM-CSF. HL60/DU-1 cells fated to die soon after terminal differentiatio n of macrophages, by 1, 25-dihydroxy vitamin D-3 treatment. We found cell d eath to be mediated mainly by necrosis, not apoptosis, as confirmed by DNA fragmentation in agarose gel electrophoresis, morphological observation und er a fluorescence microscope, and assay of lactate dehydrogenase release. E xogeneously administered GM-CSF rescued cells from necrotic death and cause d them to survive and generate superoxide anions. We also conducted immunoh istochemical analysis on an atherosclerotic human artery. Macrophages, endo thelial cells, and smooth muscle cells were found to be GM-CSF positive in an atherosclerotic lesion. In summary, GM-CSF, which is produced by macroph ages, endothelial cells, and smooth muscle cells, is thought to act in an a utocrine and a paracrine fashion as a necrosis-inhibiting factor against ar terial macrophages. This unique function may play an important role in ensu ring survival and promoting function in atherosclerotic lesions. (C) 2001 E lsevier Science Inc.