Amrit Mann, Kerstin Niekisch, Peter Schirmacher, Manfred Blessing 

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Presentation transcript:

Granulocyte–Macrophage Colony-Stimulating Factor Is Essential for Normal Wound Healing  Amrit Mann, Kerstin Niekisch, Peter Schirmacher, Manfred Blessing  Journal of Investigative Dermatology Symposium Proceedings  Volume 11, Issue 1, Pages 87-92 (September 2006) DOI: 10.1038/sj.jidsymp.5650013 Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Scab rejection postwounding. Ten transgenic animals overexpressing GM-CSF antagonist in skin and their littermate controls were wounded and observed on a daily basis for scab rejection. Note the delayed scab rejection in the transgenic animals as compared to the wild-type controls. Journal of Investigative Dermatology Symposium Proceedings 2006 11, 87-92DOI: (10.1038/sj.jidsymp.5650013) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Progress in wound healing. (a–d) Wild-type control animals as well as animals overexpressing a GM-CSF antagonist were wounded. Wounds were removed and prepared for hematoxylin/eosin staining. Five animals per genotype and time point were taken for the analysis. (a and c) Stained sections from control animals and (b and d) represent sections from the transgenic animals at 3 days (a and b) and 10 days (c and d) postwounding. Note the differences in scab formation and scab rejection, granulation tissue formation, and reepithelialization between the transgenic and the control animals. Bars: 200μm. (e) Histograph showing % reepithelialization. HE stained sections were evaluated in a double-blinded manner for the extent of reepithelialization by morphometry and % reepithelialization was quantified. Note the longer time needed by the antagonists for the complete closure of wound. Journal of Investigative Dermatology Symposium Proceedings 2006 11, 87-92DOI: (10.1038/sj.jidsymp.5650013) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Keratinocyte proliferation rates during wound healing. (a–d) Mice were injected intraperitonially with BrdUrd and killed after a labeling period of 2 hours. Sections were stained using an anti-BrdUrd antibody as described in the Materials and Methods. Five animals per genotype and time point were analyzed. Shown are (a and c) control animals and, (b and d) transgenic animals at (a and b) 3 and (c and d) 10 days postwounding, respectively. Both controls and transgenic animals exhibit a proliferative burst at 3 days postwounding; however, 10 days postwounding the transgenics exhibited significantly less numbers of proliferating kerationcytes. Bars: 200μm. (e) Histograph showing the numbers of keratinocyte S-phase nuclei at the wound margin. For this purpose BrdUrd-labeled nuclei were counted at the wound margin and related to 100 total basal cells. Enhanced but comparable rate of proliferation can be observed at 3 days postwounding in both transgenics and the control animals. At 10 days postwounding, the antagonist transgenics exhibit significantly lower proliferation rates (*P<0.05). Journal of Investigative Dermatology Symposium Proceedings 2006 11, 87-92DOI: (10.1038/sj.jidsymp.5650013) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Extent of neovascularization during the wound healing. Sections through the middle of the wounds were stained with a CD31-specific antibody for the detection of newly formed blood vesicles. The samples were photographed and the numbers of microvessels per field were counted. Five animals per genotype and time point were analyzed. Note the significantly lower numbers of microvessels in the antagonist transgenic at all the observed time points after wounding. Journal of Investigative Dermatology Symposium Proceedings 2006 11, 87-92DOI: (10.1038/sj.jidsymp.5650013) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Detection of fibrosis in the repair process. Section through the middle of wounds were cut and stained with Masson's Trichrome stain. Note the extensive collagen deposition (Blue staining) in the (b) antagonist transgenics at 14 days postwounding as compared to the (a) control animals. Bars: 200μm. Journal of Investigative Dermatology Symposium Proceedings 2006 11, 87-92DOI: (10.1038/sj.jidsymp.5650013) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions