The effect of PTX3 is dependent on Fc��RI, but in competition studies, the fibrocyte-inhibitory IPI-493 activity of SAP is dominant over PTX3. These data suggest that the relative levels of SAP and PTX3 SGI-1027 present at sites of fibrosis may have a significant effect on the ability of monocytes to differentiate into fibrocytes. We found that PTX3 promotes fibrocyte differentiation by a Fc��RI dependent mechanism. However, the fibrocyte-inhibitory activity of SAP is dominant over PTX3. In fibrotic lung tissue, we found that the distribution of PTX3 was wide spread, and present in alveolar macrophages, lung epithelial cells, and fibroblasts. However, SAP had a restricted distribution and was apparently absent from the fibrotic areas. These data suggest that the relative levels of SAP and PTX3 present at sites of fibrosis may have a significant effect on the ability of monocytes to differentiate into fibrocytes. Fibrocytes have been detected inhuman pathological conditions including pulmonary fibrosis, keloid scars, asthma, chronic kidney disease, and nephrogenic systemic fibrosis. Fibrocytes are also present in the fibrotic lesions in animal models of pulmonary fibrosis, liver fibrosis and renal fibrosis. In addition to contributing to the mass of fibrotic lesions, fibrocytes promote angiogenesis, which can then promote the growth of the lesion, and secrete TGF-��, which activates resident fibroblasts. Therefore, in situations where PTX3 is abundant and therefore available to promote fibrocyte differentiation, this may also regulate angiogenesis. Finally, the injection of mature fibrocytes into mice potentiate lung fibrosis, suggesting that the increased recruitment of monocyte-derived fibrocytes may potentiate an ongoing fibrotic response. Whether the main role of fibrocytes is to directly drive fibrosis, through the production of extracellular matrix proteins, or to act in a paracrine manner to activate stromal cells to produce more extracellular matrix proteins, or regulate angiogenesis, is still unclear. Compared to human lung tissue, the lungs of saline-treated mice expressed little PTX3.