Ricerc@Sapienza

Macrophages are an essential component of innate immunity and have a broad role in the maintenance of tissue homeostasis. Two major polarization states have been described for macrophages, the pro-inflammatory type 1 (M1) and the anti-inflammatory type 2 (M2). The ratio between M1 and M2 phenotype determines the progression and/or resolution of chronic diseases, including wounds-healing. Wounds contain macrophagic phenotypes associated with both classical and alternative activation. During the early stages of inflammation, around 85% of macrophages have an M1 phenotype. This ratio switches 5-7 days post injury where only 15-20% of macrophages have an M1 phenotype and the wound is primarily populated by M2 phenotype. Taken together, these data indicate that a better understanding of the macrophagic role in wounds-healing is still required in order to design more efficient therapeutic strategies.
In a recent in vivo study, we have demonstrated that bovine lactoferrin (bLf), a milk-derivative glycoprotein, is able to facilitate the post-surgical wound-healing in subjects suffering from bisphosphonate-related osteonecrosis of the jaws that showing the progressive destruction of bone. The results consist in a significant shorter time of wound closure (1-2 weeks), after surgical removal of the necrotic bone, compared to that observed with classical treatment (2-3 months).
Furthermore, it has been reported that, depending on M1 or M2 polarization, macrophages express at different extent a set of genes related to iron homeostasis leading to an "iron-retention" or an "iron-release" phenotype, characteristic of M1 and M2 phenotypes, respectively. Recently, we have demonstrated that bLf modulates the entire iron homeostasis machinery switching macrophages from the "iron-retention" to the "iron-release" phenotype.
Consequently, the aim of this project is a better characterization of the bLf-induced macrophagic phenotype in order to investigate its role in wound-healing.