Fibrocytes, ahematopoietic stem cell source of fibroblasts/myofibroblasts, were 
previously implicated to infiltrate into the intestinal and enhance 
inflammation.The aims of the present study were to elucidate the role of 
fibrocytes in necrotizing enterocolitis (NEC) pathogenesis and to explore the 
mechanisms by which fibrocytes contributed to the inflammatory responses.We 
investigated circulating and intestinal local fibrocytes from 32 patients with 
NEC, 8 patients with noninflammatory conditions of the gastrointestinal tract 
and 12 normal subjects.Significantly higher numbers of circulating fibrocytes 
were found in the peripheral blood from NEC patients than the controls 
(P < .01). Numerous fibrocytes were found infiltrating the NEC intestinal mucous 
membranes. The percentage of fibrocytes to total leukocytes in the NEC 
inflammatory lesions was significantly increased compared with the percentage in 
the noninflammatory gastrointestinal tract. The fibrocyte attractant chemokine 
C-X-C motif chemokine ligand 12 (CXCL12) was significantly increased in the 
plasma and was detectable in 80% of the peritoneal lavage fluid from NEC 
patients but not the controls. Furthermore, chemokine expression was increased 
in fibrocytes infiltrating and trafficking to leukocyte sites. In culture, 
lipopolysaccharide (LPS) induced a significant increase in the expression of the 
Toll-like receptor (TLR4) signal, with the upregulation of p38 in both the 
isolated fibrocytes and macrophages. Similarly, interleukin (IL)-1β induced 
increased the upregulation of the IL-6, tumor necrosis factor (TNF)-α, and 
intercellular cell adhesion molecule-1 mRNAs but downregulated ColI in 
fibrocytes isolated from NEC patients compared with the controls.These findings 
indicate that circulating fibrocytes are increased in NEC patients and may be 
recruited to the inflammatory intestinal track, most likely through the 
CXCR4/CXCL12 axis. These cells may contribute to intestinal inflammation through 
TLR4 signaling by producing the TNF-α and IL-6 cytokines.