The role of circulating fibrocytes in fibrosis.

Fibrocytes are cells that circulate in the peripheral blood and produce connective tissue proteins such as vimentin and collagens I and III. Fibrocytes are associated with skin lesions, pulmonary fibrosis, and tumors and they contribute to the remodeling response by secreting matrix metalloproteinases. Fibrocytes can further differentiate, and they are a likely source of the contractile myofibroblast that appears in many fibrotic lesions. There is evidence in the skin for a prominent role for fibrocytes in the development of hypertrophic scars and keloids. In asthma or in experimental models of pulmonary fibrosis, fibrocytes have been shown to infiltrate areas of inflammation and tissue damage. Fibrocytes constitute part of the stromal response to tumor invasion, and there is evidence that these cells may be a prognosticator of malignant potential. IL-1, TGF-beta, chemokines, and serum amyloid P modulate the appearance and function of fibrocytes. Fibrocytes themselves produce inflammatory cytokines, growth factors, and chemokines. The intercellular signals that modulate fibrocyte trafficking, proliferation, and differentiation are only partially defined, but a better understanding of these signals enable new therapies to prevent pathologic fibrosis or to improve the tissue repair response.