Mast cells modulate the inflammatory but not the proliferative response in healing wounds.
Upon stimulation, mast cells release a heterogeneous group of factors that promote inflammation and influence cell proliferation. Mast cells accumulate at sites of injury, further suggesting a critical role in wound healing. To assess the importance of mast cells in tissue repair, we compared wound healing in mast cell-deficient WBB6F1/J-KitW/KitW-v (KitW/KitW-v) and wild type WBB6F1/++ (WT) mice. During the inflammatory phase, neutrophil infiltration into wounds of the KitW/KitW-v mice was significantly less than that of WT mice (84.6 +/- 10.3 vs. 218 +/- 26.0 cells/10 high-power fields at day 3, p < 0.001), while wound macrophage and T cell infiltration were similar in both strains. The decrease in neutrophils could not be explained by changes in tumor necrosis factor-alpha or macrophage inflammatory protein-2 levels, because the amounts of these two neutrophil chemoattractants were similar in both KitW/KitW-v and WT mice. Surprisingly, the absence of mast cells had no effect on the proliferative aspects of wound healing, including reepithelialization, collagen synthesis, and angiogenesis. Although mast cells are known to release proangiogenic mediators, vascular endothelial growth factor levels were similar in WT and KitW/KitW-v mice. Moreover, levels of fibroblast growth factor-2 were increased in KitW/KitW-v mice (4206 +/- 107 vs. 1865 +/- 249 pg/ml, p < 0.01). These results suggest that mast cells modulate the recruitment of neutrophils into sites of injury, yet indicate that mast cells are unlikely to exert a major influence on the proliferative response within healing wounds.
Egozi
Eric I
EI
Burn and Shock Trauma Institute, Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Ferreira
Ahalia M
AM
Burns
Aime L
AL
Gamelli
Richard L
RL
Dipietro
Luisa A
LA
D000818:Animals; D002453:Cell Cycle / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000293:injuries*; D013997:Time Factors; D014945:Wound Healing / Q000276:immunology*; D014950:Wounds, Penetrating / Q000276:immunology*