Neuroendocrine Modulation of Cutaneous Mast Cell Maturation

Objectives: Stress delays wound healing and alters the kinetics of the early edema response. Cutaneous mast cells are important in the early development of edema during wound healing. Mast cell proliferation and maturation is regulated by growth factors and cytokines produced in local tissue. The aim of this study was to determine how stress modulates cutaneous mast cell maturation. Methods: SKH-1 female mice were subjected to restraint stress (RST) via confinement to 50 ml tubes starting 3 days before tissue biopsy. Food and water deprived mice were controls. Two 3.5mm diameter cutaneous biopsies were made on the dorsum of the animals, just rostral to the shoulder blades. The number of granulated mast cells was determined by staining histologic sections with toluidine blue. Three sections were counted for every biopsy and a total of 27 animals were assessed in each group. Histamine content of biopsied tissue was measured using a commercial ELISA (n=8 for two experiments). Real-time PCR was used to assess gene expression of growth and maturation factors for mast cells, i.e., Stem Cell Factor, IL-3, IL-9, and IL-10 Results: RST reduced the number of granulated mast cells by nearly 50% (p<0.05) compared to controls. Histamine content of tissues from RST mice was reduced by more than 50% compared to controls. (p<0.05). SCF, IL-10 and IL-3 expression was not significantly altered by stress. IL-9 expression was significantly reduced in stressed mice as compared to controls. Conclusions: Restraint-stress modulated the edema response in a mouse model of wound healing. This was associated with decreased numbers of granulated mast cells, decrease in histamine content of the tissue, and a reduced expression of a cytokine important in mast cell maturation, IL-9. Thus, stress prepares tissue for impaired early alterations in inflammation required for optimal wound healing. Supported by NIH/NIDCR DE12792 and DE13749.