Affiliation:
1. *The Picower Institute for Medical Research, Laboratory of Medical Biochemistry, Manhasset, NY 11030; and
2. †Case Western Reserve University, Department of Molecular Biology and Microbiology, Cleveland, OH 44106
Abstract
Abstract
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 these cells in vivo, we examined the expression of type I collagen and cytokine 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. Fibrocytes purified from wound chambers also were found to express mRNA for IL-1β, IL-10, TNF-α, JE/MCP, MIP-1α, MIP-1β, MIP-2, PDGF-A, TGF-β1, and M-CSF. The addition of IL-1β (1–100 ng/ml), a critical mediator in wound healing, to fibrocytes isolated from human peripheral blood induced the secretion of chemokines (MIP-1α, MIP-1β, MCP-1, IL-8, and GROα), hemopoietic growth factors (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF-α. By contrast, IL-1β decreased the constitutive secretion of type I collagen as measured by ELISA. Additional evidence for a role for fibrocytes in collagen production in vivo was obtained in studies of livers obtained from Schistosoma japonicum-infected mice. Mouse fibrocytes localized to areas of granuloma formation and connective matrix deposition. We conclude that fibrocytes are an important source of cytokines and type I collagen during both the inflammatory and the repair phase of the wound healing response. Furthermore, IL-1β may act on fibrocytes to effect a phenotypic transition between a repair/remodeling and a proinflammatory mode.
Publisher
The American Association of Immunologists
Subject
Immunology,Immunology and Allergy
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