Differential roles of macrophages in diverse phases of skin repair

Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited...

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Published in:	The Journal of immunology (1950) Vol. 184; no. 7; p. 3964
Main Authors:	Lucas, Tina, Waisman, Ari, Ranjan, Rajeev, Roes, Jürgen, Krieg, Thomas, Müller, Werner, Roers, Axel, Eming, Sabine A
Format:	Journal Article
Language:	English
Published:	United States 01.04.2010
Subjects:	Animals Cell Separation Flow Cytometry Immunohistochemistry Macrophages - physiology Mice Mice, Inbred C57BL Mice, Transgenic Reverse Transcriptase Polymerase Chain Reaction Skin - injuries Skin Physiological Phenomena Wound Healing - physiology
ISSN:	1550-6606, 1550-6606
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Abstract	Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited during the diverse phases of skin repair after mechanical injury exert specific functions to restore tissue integrity. For this purpose, we developed a mouse model that allows conditional depletion of macrophages during the sequential stages of the repair response. Depletion of macrophages restricted to the early stage of the repair response (inflammatory phase) significantly reduced the formation of vascularized granulation tissue, impaired epithelialization, and resulted in minimized scar formation. In contrast, depletion of macrophages restricted to the consecutive mid-stage of the repair response (phase of tissue formation) resulted in severe hemorrhage in the wound tissue. Under these conditions, transition into the subsequent phase of tissue maturation and wound closure did not occur. Finally, macrophage depletion restricted to the late stage of repair (phase of tissue maturation) did not significantly impact the outcome of the repair response. These results demonstrate that macrophages exert distinct functions during the diverse phases of skin repair, which are crucial to control the natural sequence of repair events.
AbstractList	Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited during the diverse phases of skin repair after mechanical injury exert specific functions to restore tissue integrity. For this purpose, we developed a mouse model that allows conditional depletion of macrophages during the sequential stages of the repair response. Depletion of macrophages restricted to the early stage of the repair response (inflammatory phase) significantly reduced the formation of vascularized granulation tissue, impaired epithelialization, and resulted in minimized scar formation. In contrast, depletion of macrophages restricted to the consecutive mid-stage of the repair response (phase of tissue formation) resulted in severe hemorrhage in the wound tissue. Under these conditions, transition into the subsequent phase of tissue maturation and wound closure did not occur. Finally, macrophage depletion restricted to the late stage of repair (phase of tissue maturation) did not significantly impact the outcome of the repair response. These results demonstrate that macrophages exert distinct functions during the diverse phases of skin repair, which are crucial to control the natural sequence of repair events. Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited during the diverse phases of skin repair after mechanical injury exert specific functions to restore tissue integrity. For this purpose, we developed a mouse model that allows conditional depletion of macrophages during the sequential stages of the repair response. Depletion of macrophages restricted to the early stage of the repair response (inflammatory phase) significantly reduced the formation of vascularized granulation tissue, impaired epithelialization, and resulted in minimized scar formation. In contrast, depletion of macrophages restricted to the consecutive mid-stage of the repair response (phase of tissue formation) resulted in severe hemorrhage in the wound tissue. Under these conditions, transition into the subsequent phase of tissue maturation and wound closure did not occur. Finally, macrophage depletion restricted to the late stage of repair (phase of tissue maturation) did not significantly impact the outcome of the repair response. These results demonstrate that macrophages exert distinct functions during the diverse phases of skin repair, which are crucial to control the natural sequence of repair events.Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited during the diverse phases of skin repair after mechanical injury exert specific functions to restore tissue integrity. For this purpose, we developed a mouse model that allows conditional depletion of macrophages during the sequential stages of the repair response. Depletion of macrophages restricted to the early stage of the repair response (inflammatory phase) significantly reduced the formation of vascularized granulation tissue, impaired epithelialization, and resulted in minimized scar formation. In contrast, depletion of macrophages restricted to the consecutive mid-stage of the repair response (phase of tissue formation) resulted in severe hemorrhage in the wound tissue. Under these conditions, transition into the subsequent phase of tissue maturation and wound closure did not occur. Finally, macrophage depletion restricted to the late stage of repair (phase of tissue maturation) did not significantly impact the outcome of the repair response. These results demonstrate that macrophages exert distinct functions during the diverse phases of skin repair, which are crucial to control the natural sequence of repair events.
Author	Roes, Jürgen Eming, Sabine A Krieg, Thomas Müller, Werner Lucas, Tina Ranjan, Rajeev Roers, Axel Waisman, Ari
Author_xml	– sequence: 1 givenname: Tina surname: Lucas fullname: Lucas, Tina organization: Department of Dermatology, University of Cologne, Cologne, Germany – sequence: 2 givenname: Ari surname: Waisman fullname: Waisman, Ari – sequence: 3 givenname: Rajeev surname: Ranjan fullname: Ranjan, Rajeev – sequence: 4 givenname: Jürgen surname: Roes fullname: Roes, Jürgen – sequence: 5 givenname: Thomas surname: Krieg fullname: Krieg, Thomas – sequence: 6 givenname: Werner surname: Müller fullname: Müller, Werner – sequence: 7 givenname: Axel surname: Roers fullname: Roers, Axel – sequence: 8 givenname: Sabine A surname: Eming fullname: Eming, Sabine A
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/20176743$$D View this record in MEDLINE/PubMed
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SubjectTerms	Animals Cell Separation Flow Cytometry Immunohistochemistry Macrophages - physiology Mice Mice, Inbred C57BL Mice, Transgenic Reverse Transcriptase Polymerase Chain Reaction Skin - injuries Skin Physiological Phenomena Wound Healing - physiology
Title	Differential roles of macrophages in diverse phases of skin repair
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