title: The phenotype of murine wound  macrophages.
abstract: The phenotype of wound macrophages has not been studied by direct examination of these cells, yet macrophages recruited to sites of injury are described as alternatively activated macrophages, requiring IL-4 or IL-13 for phenotypic expression. This study characterized wound macrophage phenotype in the PVA sponge wound model in mice. Eighty-five percent of wound macrophages isolated 1 day after injury expressed Gr-1, but only 20% of those isolated at 7 days expressed this antigen. Macrophages from 1-, 3-, and 7-day wounds expressed markers of alternative activation,including mannose receptor, dectin-1, arginase 1,and Ym1, but did not contain iNOS. Day 1 wound macrophages produced more TNF-alpha, more IL-6, and less TGF-beta than Day 7 wound macrophages. Wound macrophages did not produce IL-10. The cytokines considered necessary for alternative activation of macrophages,IL-4 and IL-13, were not detected in the wound environment and were not produced by wound cells.Wound macrophages did not contain PStat6. Wound fluids inhibited IL-13-dependent phosphorylation of Stat6 and contained IL-13Ralpha2, a soluble decoy receptor for IL-13. The phenotype of wound macrophages was not altered in mice lacking IL-4Ralpha, which is required for Stat6-dependent signaling of IL-4 and IL-13.Wound macrophages exhibit a complex phenotype,which includes traits associated with alternative and classical activation and changes as the wound matures.The wound macrophage phenotype does not require IL-4 or IL-13.
authors.affiliation: Division of Surgical Research, Rhode Island Hospital, Providence, RI 02903, USA. jdaley@lifespan.org
authors.forename: Jean M
authors.initials: JM
authors.lastname: Daley
authors.forename: Samielle K
authors.initials: SK
authors.lastname: Brancato
authors.forename: Alan A
authors.initials: AA
authors.lastname: Thomay
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Reichner
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Albina
mesh_terms: D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000032:analysis; D005122:Exudates and Transudates / Q000737:chemistry; D005547:Foreign Bodies / Q000473:pathology; D005781:Gelatin Sponge, Absorbable; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D037181:Lectins, C-Type / Q000032:analysis; D008262:Macrophage Activation; D008264:Macrophages / Q000737:chemistry* / Q000502:physiology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000032:analysis; D010641:Phenotype; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000032:analysis / Q000172:deficiency / Q000502:physiology; D019707:Receptors, Chemokine / Q000032:analysis; D050800:STAT6 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000293:injuries*; D013047:Specific Pathogen-Free Organisms; D014945:Wound Healing / Q000502:physiology*; D000099181:Dectin-1; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018793:Interleukin-13; D015847:Interleukin-4; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D050800:STAT6 Transcription Factor; D000099181:Dectin-1; C503133:Gr-1 protein, mouse; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit; C494100:Stat6 protein, mouse