Peripheral blood fibrocytes: Differentiation pathway and migration to wound sites

Fibrocytes are a distinct population of blood-borne cells that display a un ique cell surface phenotype (collagen I+/CD11b(+)/CD13(+)/CD34(+)/CD45RO(+) /MHC class II+/CD86(+)) and exhibit potent immunostimulatory activities. Ci rculating fibrocytes rapidly enter sites of tissue injury, suggesting an im portant role for these cells in wound repair. However, the regulatory proce sses that govern the differentiation of blood-borne fibrocytes and the mech anisms that underlie the migration of these cells to wound sites are curren tly not known. We report herein that ex vivo cultured fibrocytes can differ entiate from a CD14(+)-enriched mononuclear cell population and that this p rocess requires contact with T cells. Furthermore, we demonstrate that TGF- beta1 (1-10 ng/ml), an important fibrogenic and growth-regulating cytokine involved in wound healing, increases the differentiation and functional act ivity of cultured fibrocytes. Because fibrocytes home to sites of tissue in jury, we examined the role of chemokine/chemokine receptor interactions in fibrocyte trafficking. We show that secondary lymphoid chemokine, a ligand of the CCR7 chemokine receptor, acts as a potent stimulus for fibrocyte che motaxis in vitro and for the homing of injected fibrocytes to sites of cuta neous tissue injury in vivo. Finally, we demonstrate that differentiated, c ultured fibrocytes express a smooth muscle actin and contract collagen gels in vitro, two characteristic features of wound-healing myofibroblasts. The se data provide important insight into the control of fibrocyte differentia tion and trafficking during tissue repair and significantly expand their po tential role during wound healing.