title: Catalase plays a critical role in the CSF-independent survival of human macrophages via regulation of the expression of BCL-2 family.
abstract: M-colony-stimulating factor (M-CSF)-induced monocyte-derived macrophages (M-Mphi) required continuous presence of M-CSF for their survival, and depletion of M-CSF from the culture induced apoptosis, whereas human alveolar macrophages (A-Mphi) and granulocyte-macrophage (GM)-CSF-induced monocyte-derived macrophages (GM-Mphi) survived even in the absence of CSF. The expression of BCL-2 was higher in M-Mphi, and M-CSF withdrawal down-regulated the expression. The expression of BCL-X(L) was higher in A-Mphi and GM-Mphi, and the expression was CSF-independent. The expression of MCL-1 and BAX were not different between M-Mphi and GM-Mphi and were CSF-independent. Down-regulation of the expression of BCL-2 and BCL-X(L) by RNA interference showed the important role of BCL-2 and BCL-X(L) in the survival of M-Mphi and GM-Mphi, respectively. Human erythrocyte catalase (HEC) and conditioned medium obtained from GM-Mphi or A-Mphi cultured in the absence of GM-CSF prevented the M-Mphi from apoptosis and restored the expression of BCL-2. The activity of the conditioned medium was abrogated by pretreatment with anti-HEC antibody. Anti-HEC antibody also induced the apoptosis of M-Mphi cultured in the presence of M-CSF and GM-Mphi and A-Mphi cultured in the presence or absence of GM-CSF and down-regulated the expression of BCL-2 and BCL-X(L) in these Mphis. GM-Mphi and A-Mphi, but not M-Mphi, can produce both extracellular catalase and cell-associated catalase in a CSF-independent manner. Intracellular glutathione levels were kept equivalent in these Mphis, both in the presence or absence of CSF. These results indicate a critical role of extracellular catalase in the survival of human macrophages via regulation of the expression of BCL-2 family genes.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Komuro
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Aikichi
authors.initials: A
authors.lastname: Iwamoto
authors.forename: Kiyoko S
authors.initials: KS
authors.lastname: Akagawa
mesh_terms: D017209:Apoptosis; D015152:Blotting, Northern; D002374:Catalase / Q000378:metabolism / Q000502:physiology*; D002452:Cell Count; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004912:Erythrocytes / Q000201:enzymology; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012313:RNA / Q000737:chemistry; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013438:Sulfhydryl Compounds; D051020:bcl-X Protein; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor; D002374:Catalase; D005978:Glutathione