Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2005
Publication Date: 12/1/2005
Citation: Olutoye, O.O., Zhu, X., Cass, D.L., Smith, C.W. 2005. Neutrophil recruitment by fetal procine endothelial cells: Implications in scarless fetal wound healing. Pediatric Research. 58:1290-1294. Interpretive Summary: In order to lay the groundwork for future studies of dietary effects on wound healing in mother and fetus, we have undertaken a study of the differences in wound healing in the mother and fetus in a pig model. In this basic cell biology paper, we have demonstrated that the cells that line the blood vessels (endothelial cells) function differently in the fetus than in the adult. The fetal cells are far less efficient in supporting the attachment of white blood cells. This attachment is necessary before white blood cells can leave the blood and migrate into tissue. In the adult this process in necessary to fight infection, but can cause damage to tissues. Since the fetus is in a sterile environment, there is little need for this migration and it appears that the endothelial cells help to reduce migration of white cells into tissue. Thus, the functions of this process may be very different in the mother and fetus, raising cautions when attempting to modulate the process either with drugs or through dietary manipulations.
Technical Abstract: Fetal dermal wounds heal scarlessly and with a minimal inflammatory response. When a robust inflammatory response is induced at the site of fetal dermal wounds by the application of cytokines, healing results in fibrosis. To test the hypothesis that the reduced inflammatory response in fetal wounds is due to impaired fetal leukocyte-endothelial interactions, the contributions of fetal endothelial cells to the inflammatory response in the fetus were investigated. Endothelial cells isolated from blood vessels of adult and mid-gestational fetal pigs were cultured in media until confluent monolayers were established. Adult porcine neutrophils were isolated and resuspended at a concentration of 1 million cells/mL. Interactions between neutrophils and endothelial cells were observed under static and flow conditions. Endothelial monolayers were exposed to neutrophils with and without prior stimulation of the endothelial cells with tumor necrosis factor alpha (TNF-alpha) for 4 h. The neutrophil-endothelial interactions were observed and analyzed for neutrophil adhesion, rolling velocity, and transmigration. Endothelial P-selectin mRNA expression was determined by real-time polymerase chain reaction (PCR). A novel in vitro model of fetal inflammation is described. Both adult and fetal endothelial cells demonstrated a dose-dependent increase in neutrophil adhesion and transmigration with increasing doses of TNF-alpha. The fetal response was significantly lower than the adult. As expected, rolling velocity was lower at higher cytokine concentrations and had an inverse correlation with P-selectin mRNA expression. Fetal endothelial cells are less permissive to adhesion and transmigration of neutrophils than adult endothelial cells. This may contribute to the paucity of inflammation seen in the fetal response to dermal injury.