title: A novel subpopulation of peripheral blood mononuclear cells presents in major burn patients.
abstract: Hypertrophic scars (HTS) are generally believed to result from proliferation and activation of resident connective tissue fibroblasts after burns. To demonstrate a potential role of blood-borne cells, the peripheral blood mononuclear cells (PBMCs) and the effect of PBMCs on dermal fibroblast behavior was investigated. Flow cytometry was used to analyze the surface and intracellular protein expression of PBMCs and fibroblasts. Transwell migration assay, enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction was performed to assess fibroblast functions. We identified a novel subpopulation of PBMCs in burn patients in vivo that appears at an early stage following major thermal injuries, which primarily express procollagen 1, leukocyte specific protein 1, CD204, toll-like receptor 4 and stromal cell-derived factor 1 (SDF-1) receptor CXCR4. In vitro, the conditioned media from burn patient PBMCs up-regulated the expression of fibrotic growth factors and extracellular matrix molecules, down-regulated antifibrotic factor decorin, enhanced cell chemotaxis and promoted cell differentiation into contractile myofibroblasts in dermal fibroblasts. After thermal injury, this novel subpopulation of PBMCs is systemically triggered and attracted to the wounds under SDF-1/CXCR4 signaling where they appear to modulate the functions of resident connective tissue cells and thus contribute to the development of HTS.
authors: Wound Healing Research Group, Division of Plastic and Reconstructive Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7.
authors: Hongbin
authors: H
authors: Liu
authors: Wound Healing Research Group, Division of Plastic and Reconstructive Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7.
authors: Jie
authors: J
authors: Ding
authors: Wound Healing Research Group, Division of Plastic and Reconstructive Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7; Division of Critical Care Medicine, Department of Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7.
authors: Zengshuan
authors: Z
authors: Ma
authors: Wound Healing Research Group, Division of Plastic and Reconstructive Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7; Division of Critical Care Medicine, Department of Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7.
authors: Zhenshen
authors: Z
authors: Zhu
authors: Wound Healing Research Group, Division of Plastic and Reconstructive Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7.
authors: Heather A
authors: HA
authors: Shankowsky
authors: Wound Healing Research Group, Division of Plastic and Reconstructive Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7; Division of Critical Care Medicine, Department of Surgery, University of Alberta, 2D2.28 WMC, 8440-112 Street, Edmonton, AB, Canada T6G 2B7. Electronic address: etredget@ualberta.ca.
authors: Edward E
authors: EE
authors: Tredget
mesh_terms: D000328:Adult; D001830:Body Surface Area; D002056:Burns / Q000097:blood* / Q000473:pathology; D002454:Cell Differentiation; D054443:Cell Migration Assays; D002478:Cells, Cultured; D002633:Chemotaxis; D017439:Cicatrix, Hypertrophic / Q000097:blood*; D003239:Connective Tissue Cells / Q000166:cytology / Q000378:metabolism; D058575:Decorin / Q000378:metabolism; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D058628:Myofibroblasts / Q000166:cytology; D011347:Procollagen / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000166:cytology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015599:Trauma Severity Indices; D055815:Young Adult
chemical_list: C527276:CXCR4 protein, human; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C489183:LSP1 protein, human; C495139:MSR1 protein, human; D008840:Microfilament Proteins; D011347:Procollagen; D019718:Receptors, CXCR4; D051117:Scavenger Receptors, Class A; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Burn injury; Fibrocytes; Hypertrophic scars; Macrophages