Monocyte/Macrophage MMP-14 Modulates Cell Infiltration and T-Cell Attraction in Contact Dermatitis But Not in Murine Wound Healing

Abstract

Monocyte infiltration and subsequent differentiation into macrophages has been shown to be crucial during inflammation. Metalloproteinases are key enzymes in these processes, but the role of MMP-14 remains largely unknown. To address this question, we generated animals with conditional ablation of MMP-14 in the monocyte/macrophage lineage. The knockout (KO) animals (LysM-Cre(+)MMP-14(fl/fl)) were healthy and fertile, and neither skin architecture nor differentiation was altered from the wild type (WT). Full-thickness wounds were induced, and careful analysis of wound closure, granulation tissue formation, and angiogenesis revealed no differences between genotypes. The inflammatory response, monocyte influx, differentiation, and lymphocyte infiltration was also similar in KO and WT animals. Ear swelling after croton oil application was similar in the KO and WT animals. Interestingly, the number of monocytes and macrophages, as well as of T cells, was significantly reduced in KO animals, compared with WT animals. Similarly, both P-selectin and proinflammatory cytokine levels were markedly reduced in KO animals. In vitro, the migratory capacity of isolated KO macrophages was significantly impaired on fibronectin, a substrate of MMP-14. These data point to a role of MMP-14 during transendothelial migration of monocytes and T-cell attraction.