Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 175, Issue 1, Pages 132-147Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2009.081002
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFBs 553, SFBs 815, FR 1540/1, FR 1540/2, GK 1172]
Ask authors/readers for more resources
Whether the wound macrophage is a key regulatory inflammatory cell type in skin repair has been a matter of debate. A transgenic mouse model mediating inducible macrophage depiction during skin repair has not been used to date to address this question. Here, we specifically rendered the monocyte/macrophage leukocyte lineage sensitive to diphtheria toxin by expressing the lysozyme M promoter-driven, Cre-mediated excision of a transcriptional STOP cassette from the simian DT receptor gene in mice (lysM-Cre/DTR). Application of diphtheria toxin to lysM-Cre/DTR mice led to a rapid reduction in both skin tissue and wound macrophage numbers at sites of injury. Macrophage-depleted mice revealed a severely impaired wound morphology and delayed healing. in the absence of macrophages, wounds were re-populated by large numbers of neutrophils. Accordingly, macrophage-reduced wound tissues exhibited the increased and prolonged persistence of macrophage inflammatory protein-2, macrophage chemoattractant protein-1, interleukin-1 beta, and cyclooxygenase-2, paralleled by unaltered levels of bioactive transforming growth factor-beta 1. Altered expression patterns of vascular endothelial growth factor on macrophage reduction were associated with a disturbed neo-vascularization at the wound site. Impaired wounds revealed a loss of myofibroblast differentiation and wound contraction. Our data in the use of lysM-Cre/DTR mice emphasize the pivotal function of wound macrophages in the integration of inflammation and cellular movements at the wound site to enable efficient skin repair. (Am J Pathol 2009, 175:132-147; DOI: 10.2353/ajpath.2009.081002)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available