Wound healing in the PU.1 null mouse--tissue repair is not dependent on inflammatory cells.
Damage to neonatal and adult tissues always incites an influx of inflammatory neutrophils and macrophages. Besides clearing the wound of invading microbes, these cells are believed to be crucial coordinators of the repair process, acting both as professional phagocytes to clear wound debris and as a major source of wound growth factor signals. Here we report wound healing studies in the PU.1 null mouse, which is genetically incapable of raising the standard inflammatory response because it lacks macrophages and functioning neutrophils. Contrary to dogma, we show that these "macrophageless" mice are able to repair skin wounds with similar time course to wild-type siblings, and that repair appears scar-free as in the embryo, which also heals wounds without raising an inflammatory response. The growth factor and cytokine profile at the wound site is changed, cell death is reduced, and dying cells are instead engulfed by stand-in phagocytic fibroblasts. We also show that hyperinnervation of the wound site, previously believed to be a consequence of inflammation, is present in the PU.1 null wound, too.
Martin
Paul
P
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom. paul.martin@ucl.ac.uk
D'Souza
Deana
D
Martin
Julie
J
Grose
Richard
R
Cooper
Lisa
L
Maki
Rich
R
McKercher
Scott R
SR
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D012260:Ribonucleases; D012879:Skin Physiological Phenomena; D015534:Trans-Activators / Q000172:deficiency*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D016207:Cytokines; D011518:Proto-Oncogene Proteins; D012260:Ribonucleases; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000099232:Proto-Oncogene Protein Spi-1