Contributions of fetal leukocytes and endothelial cells in scarless fetal wound healing

Abstract

Abstract Introduction: Scarless fetal dermal wound healing progresses rapidly, without the acute inflammatory response typical of adult wound healing. To better understand the factors surrounding the reduced fetal inflammatory response, we investigated the mechanisms of leukocyte trafficking in an in-vitro model. We hypothesized that the minimal inflammatory response in fetal wounds is due to impaired leukocyte endothelial interaction in the fetus. Methods: Endothelial cells (EC) were harvested from veins of fetal (day 60; term=115 days) and adult pigs. Confluent primary endothelial monolayers were activated with porcine IL-1 beta 100ng/ml and exposed to a suspension of adult and fetal leukocytes in a continuous flow system with a shear stress of 2 dynes/cm2. Adhesion of leukocytes to the ECs was quantified and compared. Student's t-test was utilized for statistics with ∗p Results: Significantly more adult leukocytes adhered to adult ECs than fetal ECs (207+/-10 vs 89+/-4 cells/mm2). Fetal leukocytes were more likely to adhere to adult EC but this was not significant (45+/-5 vs 30+/-9). Both adult and fetal ECs were more likely to attract adult leukocytes than fetal leukocytes. The number of adult leukocytes adherent to adult ECs was seven times the fetal leukocytes adherent to fetal ECs (207+/-10 vs 30+/-9) and this was significant. Conclusions: Leukocyte-endothelial interaction in the fetus is less efficient than in the adult. This impairment appears to be due to limitations in both leukocyte and endothelial function and may explain, in part, the differences in inflammatory response in fetal and adult wounds.