The role of mast cells in cellular modifications evoked by Exendin-4 in treated wounds: a preclinical study

Aims: We studied the response of cellular infiltration in wounds treated with Exendin-4. Methods: Sixteen mice were used in the study. Two wounds were simulated, one above the other on each of the mice. The wounds then received an intradermal injection of: Saline (20 μl; Group 1) or Exendin-4 (62 ng; Group 2) in the upper and lower wounds, respectively. The mice were sacrificed in order to collect the wounds at time of abrasion (T0), 48 h (T1), 96 h (T2) and 144 h (T3). The expression of the glucagon-like peptide-1 receptor was evaluated by Western-blot in wound lysates. Histological and histochemistry methods were applied in cryosections. Results: In T2 and T3 treated wounds the mast cells degranulation index increased while GLP1-R expression, TNFalpha, or HSP47 antigens were detected in their cytoplasm. These cells interacted with dendritic cells, vessels, or granulocytes. Dendritic cells increased progressively and intercellular connections were found between these cells and vessels. Among the dendritic cells at T2 only M2 macrophages increased. However, M1 cells expressed TGFbeta and both interacted with either fibroblasts or with vessels. The number of plasmacytoid dendritic cells increased and established close contacts with regulatory T cells. Conclusion: We propose that after treatment with Exe-4. early activation of mast cells is critical in wound healing acceleration This is crucial in understanding the potential effect of this drug for viable clinical therapies.