title: Group-II phospholipase A(2) enhances oxidized low density lipoprotein-induced macrophage growth through enhancement of GM-CSF release.
abstract: Inflammatory process plays an important role in the development and progression of atherosclerotic lesions. Recently, group-II phospholipase A(2) (PLA(2)), an inflammatory mediator, was reported to exist in human atherosclerotic lesions and to enhance the development of murine atherosclerotic lesions. Oxidized low density lipoprotein (Ox-LDL) stimulates the growth of several types of macrophages in vitro. Since proliferation of macrophages occurs in atherosclerotic lesions, it is possible to assume that the Ox-LDL-induced macrophage proliferation might be involved in the progression of atherosclerosis. In this study, the role of group-II PLA(2) in the Ox-LDL-induced macrophage growth was investigated using thioglycollate-elicited mouse peritoneal macrophages. Thioglycollate-elicited macrophages significantly expressed group-II PLA(2) and released it into the culture medium. The Ox-LDL-induced thymidine incorporation into thioglycollate-elicited macrophages was three times higher than that into resident macrophages, whereas under the same conditions, granulocyte/macrophage colony-stimulating factor (GM-CSF) equally induced thymidine incorporation into both types of macrophages. Moreover, the Ox-LDL-induced GM-CSF release from thioglycollate-elicited macrophages was significantly higher than that from resident macrophages. In addition, the Ox-LDL-induced thymidine incorporation into macrophages obtained from human group-II PLA(2) transgenic mice and the GM-CSF release from these cells were significantly higher than those from their negative littermates, and the Ox-LDL-induced thymidine incorporation into human group-II PLA(2) transgenic macrophages was significantly inhibited by a polyclonal anti-human group-II PLA(2) antibody. These results suggest that the expression of group-II PLA(2) in thioglycollate-elicited macrophages may play an enhancing role in the Ox-LDL-induced macrophage growth through the enhancement of the GM-CSF release.
authors.affiliation: Department of Metabolic Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, 860-8556, Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kaneko
authors.forename: M
authors.initials: M
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Matsumura
authors.forename: T
authors.initials: T
authors.lastname: Biwa
authors.forename: N
authors.initials: N
authors.lastname: Furukawa
authors.forename: T
authors.initials: T
authors.lastname: Shirotani
authors.forename: S
authors.initials: S
authors.lastname: Kiritoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Anami
authors.forename: K
authors.initials: K
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Sasahara
authors.forename: M
authors.initials: M
authors.lastname: Shichiri
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D054501:Group II Phospholipases A2; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010741:Phospholipases A / Q000502:physiology*; D013864:Thioglycolates / Q000494:pharmacology
chemical_list: D008077:Lipoproteins, LDL; D013864:Thioglycolates; C099252:oxidized low density lipoprotein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010741:Phospholipases A; D054501:Group II Phospholipases A2