title: Selective M2 Macrophage Depletion Leads to Prolonged Inflammation in Surgical Wounds.
abstract: BACKGROUND
  A prolonged inflammatory phase is seen in aberrant wound healing and in chronic wounds. Macrophages are central to wound healing. Distinct macrophage subtypes have differing roles both in initial inflammation and in later tissue repair. Broadly, these cells can be divided into M1 and M2 macrophages. M2 macrophage proliferation and differentiation is regulated by colony-stimulating factor 1 (CSF-1) signalling and can be blocked by GW2580, a competitive cFMS kinase inhibitor, thereby allowing for analysis of the effect of M2 blockade on progression of surgical wounds.
  
  
  METHODS
  Macrophage Fas-induced apoptosis (MaFIA) transgenic mice with a macrophage-specific promoter used to express green fluorescent protein (GFP) were used to allow for cell tracking. The animals were treated by oral gavage with GW2580. Surgical wounds were created and harvested after 2 weeks for analysis.
  
  
  RESULTS
  GW2580-treated mice had significantly more GFP+ cells in the surgical scar than vehicle-treated animals (GW2580, 68.0 ± 3.1%; vehicle, 42.8 ± 1.7%; p < 0.001), and GW2580 treatment depleted CD206+ M2 macrophages in the scar (GW2580, 1.4%; vehicle, 19.3%; p < 0.001). Treated animals showed significantly higher numbers of neutrophils (vehicle, 18.0%; GW2580, 51.3%; p < 0.01) and M1 macrophages (vehicle, 3.8%; GW2580, 12.8%; p < 0.01) in the scar compared to vehicle-treated animals. The total collagen content in the area of the scar was decreased in animals treated with GW2580 as compared to those treated with vehicle alone (GW2580, 67.1%; vehicle, 79.9%; p < 0.005).
  
  
  CONCLUSIONS
  Depletion of M2 macrophages in surgical wounds via CSF-1 signalling blockade leads to persistent inflammation, with an increase in neutrophils and M1 macrophages and attenuated collagen deposition.
authors.affiliation: Centre for Research in Vascular Biology, University College Cork, Cork, Ireland.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Klinkert
authors.forename: Derek
authors.initials: D
authors.lastname: Whelan
authors.forename: Anthony J P
authors.initials: AJP
authors.lastname: Clover
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Leblond
authors.forename: Arun H S
authors.initials: AHS
authors.lastname: Kumar
authors.forename: Noel M
authors.initials: NM
authors.lastname: Caplice
mesh_terms: D000818:Animals; D000840:Anisoles; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011743:Pyrimidines; D000072836:Surgical Wound / Q000276:immunology*; D014945:Wound Healing / Q000276:immunology*
chemical_list: C506269:5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine; D000840:Anisoles; D011743:Pyrimidines
keywords: Macrophages; Surgical wound; Wound healing