Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2-deficient mice (CCR2-/- ) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2-/- and WT mice revealed a significant decrease in inflammatory, Ly6CHi recruited monocyte/macrophages in CCR2-/- wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2-/- wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2+/+ and CCR2-/- mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2+/+ and CCR2-/- mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2-deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:48 |
|---|---|
| Enthalten in: |
European journal of immunology - 48(2018), 9 vom: 07. Sept., Seite 1445-1455 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Boniakowski, Anna E [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Ccr2 protein, mouse |
|---|
| Anmerkungen: |
Date Completed 05.03.2019 Date Revised 06.03.2020 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/eji.201747400 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM28524048X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM28524048X | ||
| 003 | DE-627 | ||
| 005 | 20231225045015.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/eji.201747400 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0950.xml |
| 035 | |a (DE-627)NLM28524048X | ||
| 035 | |a (NLM)29879295 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Boniakowski, Anna E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 05.03.2019 | ||
| 500 | |a Date Revised 06.03.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2-deficient mice (CCR2-/- ) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2-/- and WT mice revealed a significant decrease in inflammatory, Ly6CHi recruited monocyte/macrophages in CCR2-/- wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2-/- wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2+/+ and CCR2-/- mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2+/+ and CCR2-/- mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2-deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Chemokine receptor | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a Recruitment | |
| 650 | 4 | |a Wound healing | |
| 650 | 7 | |a Ccr2 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, CCR2 |2 NLM | |
| 700 | 1 | |a Kimball, Andrew S |e verfasserin |4 aut | |
| 700 | 1 | |a Joshi, Amrita |e verfasserin |4 aut | |
| 700 | 1 | |a Schaller, Matt |e verfasserin |4 aut | |
| 700 | 1 | |a Davis, Frank M |e verfasserin |4 aut | |
| 700 | 1 | |a denDekker, Aaron |e verfasserin |4 aut | |
| 700 | 1 | |a Obi, Andrea T |e verfasserin |4 aut | |
| 700 | 1 | |a Moore, Bethany B |e verfasserin |4 aut | |
| 700 | 1 | |a Kunkel, Steve L |e verfasserin |4 aut | |
| 700 | 1 | |a Gallagher, Katherine A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of immunology |d 1971 |g 48(2018), 9 vom: 07. Sept., Seite 1445-1455 |w (DE-627)NLM000108723 |x 1521-4141 |7 nnns |
| 773 | 1 | 8 | |g volume:48 |g year:2018 |g number:9 |g day:07 |g month:09 |g pages:1445-1455 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/eji.201747400 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 48 |j 2018 |e 9 |b 07 |c 09 |h 1445-1455 | ||