title: CCL17 and IL-10 as effectors that enable alternatively activated macrophages to inhibit the generation of classically activated macrophages.
abstract: Classically activated macrophages (CAMphi) have been described as a major effector cell on the host's innate immunities. However, CAMphi are not generated in immunocompromised hosts whose alternatively activated macrophages (AAMphi) predominate. In this study, the mechanism by which AAMphi suppress the ability of resident macrophages (RMphi) to generate CAMphi was investigated. AAMphi were isolated from peritoneal exudates of mice 2 days after third-degree thermal injuries affecting 15% total body surface area. CAMphi were generated from RMphi (peritoneal Mphi from normal mice) through stimulation with CpG DNA, a typical CAMphi inducer. RMphi did not polarize to CAMphi when they were cultured with AAMphi in a dual-chamber Transwell even when supplemented with CpG DNA. In addition, RMphi stimulated with CpG DNA did not convert to CAMphi when they were cultured with the culture fluids of AAMphi (AAMphi Culture-Sup). AAMphi Culture-Sup contained IL-6, IL-10, CCL17, PGE(2), and TGF-beta. Among these, CCL17 and IL-10 inhibited CAMphi generation. The ability of AAMphi Culture-Sup to inhibit CAMphi generation was eliminated when the Culture-Sup was treated with a mixture of mAbs directed against CCL17 and IL-10. These results indicate that CCL17 and IL-10 released from AAMphi inhibit CAMphi generation from RMphi stimulated with CpG DNA.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Katakura
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology / Q000473:pathology; D002449:Cell Aggregation / Q000276:immunology; D002478:Cells, Cultured; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology*; D018920:Coculture Techniques; D018899:CpG Islands / Q000276:immunology; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology*; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012995:Solubility
chemical_list: C106230:CCL17 protein, human; C408982:CPG-oligonucleotide; C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; D017077:Culture Media, Conditioned; D009838:Oligodeoxyribonucleotides; D016753:Interleukin-10