REGULATED PRODUCTION OF TYPE-I COLLAGEN AND INFLAMMATORY CYTOKINES BYPERIPHERAL-BLOOD FIBROCYTES

We recently described a novel population of blood-borne cells, termed fibrocytes, that display a distinct cell surface phenotype (collagen()/CD13(+)/CD34(+)/CD45(+)), rapidly enter sites of tissue injury, and contribute to scar formation. To further characterize the role of thes e cells in vivo, we examined the expression of type I collagen and cyt okine mRNAs by cells isolated from wound chambers implanted into mice. Five days after chamber implantation, CD34(+) fibrocytes but not CD14 (+) monocytes or CD90(+) T cells expressed mRNA for type I collagen. F ibrocytes purified from wound chambers also were found to express mRNA for IL-1 beta, IL-10, TNF-alpha, JE/MCP, MIP-1 alpha, MIP-1 beta, MIP -2, PDGF-A, TGF-beta 1, and M-CSF. The addition of IL-1 beta (1-100 ng /ml), a critical mediator in wound healing, to fibrocytes isolated fro m human peripheral blood induced the secretion of chemokines (MIP-1 al pha, MIP-1 beta, MCP-1, IL-8, and GRO alpha), hemopoietic growth facto rs (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF- alpha. By contrast, IL-1 beta decreased the constitutive secretion of type I collagen as measured by ELISA. Additional evidence for a role f or fibrocytes in collagen production in vivo was obtained in studies o f livers obtained from Schistosoma japonicum-infected mice. Mouse fibr ocytes localized to areas of granuloma formation and connective matrix deposition. We conclude that fibrocytes are an important source of cy tokines and type I collagen during both the inflammatory and the repai r phase of the wound healing response. Furthermore, IL-1 beta may act on fibrocytes to effect a phenotypic transition between a repair/remod eling and a proinflammatory mode.