title: Modulation of macrophage recruitment into wounds by monocyte chemoattractant protein-1.
abstract: Previous studies suggest that normal wound repair requires the regulated production of monocyte and macrophage chemoattractants. The current study examines the role of monocyte chemoattractant protein-1 (MCP-1) in coordinating monocyte recruitment into sites of injury. MCP-1 protein was detected in both incisional and excisional murine wounds, with a peak concentration occurring slightly before maximum macrophage infiltration. Compared to wounds treated with control antibody, wounds treated with a neutralizing monoclonal anti-MCP-1 antibody contained significantly fewer macrophages (8.2 +/- 0.9 vs. 14 +/- 1.7 macrophages per high power field, p < 0.05). Conversely, the addition of recombinant MCP-1 to wounds resulted in a substantial increase in the number of macrophages (107% to 124% increase over untreated wounds, p < 0.01). Because macrophages promote wound healing, the effect of recombinant MCP-1 on the wound healing process was examined. Incisional wounds (n = 12) were either left untreated or treated with vehicle alone, 5 ng recombinant MCP-1 in vehicle, or 50 ng recombinant MCP-1 in vehicle. Wound disruption strength was determined on days 7, 14, 21, and 28 for each group. Wounds treated with MCP-1 exhibited a slight increase in wound disruption strength at nearly all time points but this increase did not reach statistical significance. Addition of 100 ng of MCP-1 to excisional wounds did not have any significant effect on wound reepithelialization. Taken together, the results show that MCP-1 is produced within wounds at physiologic concentrations, and is an important positive regulator of macrophage recruitment into sites of injury. Addition of exogenous MCP-1 to wounds of normal mice yields only modest enhancement of the repair process.
authors.affiliation: Burn and Shock Trauma Institute, Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153, USA. ldipiet@luc.edu
authors.forename: L A
authors.initials: LA
authors.lastname: Dipietro
authors.forename: M G
authors.initials: MG
authors.lastname: Reintjes
authors.forename: Q E
authors.initials: QE
authors.lastname: Low
authors.forename: B
authors.initials: B
authors.lastname: Levi
authors.forename: R L
authors.initials: RL
authors.lastname: Gamelli
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D012680:Sensitivity and Specificity; D012867:Skin / Q000293:injuries*; D014945:Wound Healing / Q000187:drug effects; D014950:Wounds, Penetrating / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D011994:Recombinant Proteins