Regulated production of type I collagen and inflammatory cytokines by peripheral 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 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-1beta, IL-10, TNF-alpha, JE/MCP, MIP-1alpha, MIP-1beta, MIP-2, PDGF-A, TGF-beta1, and M-CSF. The addition of IL-1beta (1-100 ng/ml), a critical mediator in wound healing, to fibrocytes isolated from human peripheral blood induced the secretion of chemokines (MIP-1alpha, MIP-1beta, MCP-1, IL-8, and GRO alpha), hemopoietic growth factors (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF-alpha. By contrast, IL-1beta 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-1beta may act on fibrocytes to effect a phenotypic transition between a repair/remodeling and a proinflammatory mode.
Chesney
J
J
The Picower Institute for Medical Research, Laboratory of Medical Biochemistry, Manhasset, NY 11030, USA.
Metz
C
C
Stavitsky
A B
AB
Bacher
M
M
Bucala
R
R
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001773:Blood Cells / Q000378:metabolism*; D018925:Chemokines / Q000096:biosynthesis; D003094:Collagen / Q000096:biosynthesis*; D003239:Connective Tissue Cells / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression; D006099:Granuloma / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D012554:Schistosomiasis japonica / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014945:Wound Healing
D018952:Antigens, CD34; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D003094:Collagen