Related Experiment Video
Updated: Aug 7, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Adriamycin promotes macrophage dysfunction in mice
Reto Asmis1, Mu Qiao, Randall R Rossi
1Division of Nephrology, University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System, 7703 Floyd Curl Drive, MSC 7882, San Antonio, TX 78229, USA. asmis@uthscsa.edu
Abstract:
Impaired wound healing contributes to the morbidity and mortality associated with adriamycin chemotherapy. Macrophages are essential for tissue repair and loss of macrophage function leads to impaired wound healing. We recently showed that adriamycin is a potent inducer of thiol oxidation and cell injury in cultured macrophages (FASEB J. 19:1866-1868; 2005). Here we tested the hypothesis that adriamycin also promotes oxidative stress and macrophage dysfunction in vivo. We treated FVB mice twice a week either with low doses of adriamycin (4 mg/kg) or with the same volume of saline by tail vein injection for a total of 8 injections. Wound healing was significantly delayed in adriamycin-treated mice. The number of resident peritoneal macrophages was decreased by 30% and macrophage recruitment in response to thiogycolate stimulation was decreased by 46% in mice treated with adriamycin. LPS-induced TNFalpha and IL-1beta secretion from macrophages of adriamycin-treated mice was decreased by 28.7 and 29.5%, respectively, compared to macrophages isolated from saline-injected mice. Peritoneal macrophages isolated from adriamycin-treated mice also showed increased formation of reactive oxygen species and enhanced protein-S-glutathionylation. In summary, our results show that low cumulative doses of adriamycin are sufficient both to promote sustained thiol oxidative stress and macrophage dysfunction in vivo and to delay tissue repair, suggesting that macrophage dysfunction contributes to impaired wound healing associated with adriamycin chemotherapy.
Insights
Adriamycin chemotherapy impairs wound healing by causing oxidative stress and macrophage dysfunction. This study shows low adriamycin doses reduce macrophage numbers and function, delaying tissue repair in mice.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Impaired wound healing is a significant complication of adriamycin chemotherapy.
- Macrophages are critical for tissue repair, and their dysfunction can impede healing.
- Previous research indicated adriamycin induces oxidative stress in cultured macrophages.
Purpose of the Study:
- To investigate if adriamycin induces oxidative stress and macrophage dysfunction in vivo.
- To determine the effect of adriamycin on wound healing in a mouse model.
- To explore the link between adriamycin-induced macrophage dysfunction and delayed tissue repair.
Main Methods:
- FVB mice received low-dose adriamycin or saline injections twice weekly for 8 weeks.
- Wound healing was assessed in treated and control mice.
- Macrophage populations, recruitment, cytokine secretion (TNF-alpha, IL-1beta), reactive oxygen species (ROS) formation, and protein-S-glutathionylation were analyzed.
Main Results:
- Adriamycin treatment significantly delayed wound healing.
- A decrease in resident peritoneal macrophages and impaired macrophage recruitment was observed.
- Adriamycin-treated mice showed reduced LPS-induced TNF-alpha and IL-1beta secretion.
- Macrophages from adriamycin-treated mice exhibited increased ROS production and protein-S-glutathionylation.
Conclusions:
- Low cumulative doses of adriamycin induce sustained thiol oxidative stress and macrophage dysfunction in vivo.
- Adriamycin-impaired macrophage function contributes to delayed tissue repair.
- Targeting macrophage dysfunction may improve wound healing in patients undergoing adriamycin chemotherapy.
