Decreased adhesion of polymorphonuclear cells (PMNs) to endothelial cells(ECs) and delayed transendothelial cell migration have been consistently reported in neonates. Previous studies that focused on abnormalities of neonatal PMNs have failed to completely define the nature of this defect. We studied the developmental expression of EC adhesion molecules to determine if their expression is decreased in newborns. Adult and newborn Sprague-Dawley rats were injected intraperitoneally with either buffer or thioglycollate. After 4 hours, they were sacrificed and their peritoneum lavaged. The increase in peritoneal PMNs was 5x greater in adult than newborn rats (p=0.01). To determine if decreased expression of EC adhesion molecules contributed to the delay in PMN transmigration, we isolated leukocytes from adult rats, labeled them with 111Indium and injected them systemically into newborn and adult rats. The transmigration of adult leukocytes was measured by counting the radioactivity in the peritoneal lavage following intraperitoneal injection of thioglycollate. Again, the increase in peritoneal leukocytes was 5x greater in adult than newborn rats (p=0.05). This indicated that defects in neonatal PMNs could not completely account for delayed transmigration. To determine if delayed expression of EC adhesion molecules contributed to decreased transmigration, we performed immunohistochemical analysis of mesentery isolated from the rats used in the above experiments. There was no difference in the expression of PECAM-1 or ICAM-1 in adult and newborn rats; however, the endothelium from adult but not newborn rats stained positively for P-selectin. To determine if the synthesis of P-selectin increases with maturity in humans, we obtained human umbilical vein endothelial cells (HUVECs) from preterm(<32 weeks) and term (>38 weeks) umbilical cords. The HUVECs were lysed immediately after isolation and the concentration of cell adhesion molecules was determined in the cell lysates by ELISA. The P-selectin concentration was significantly greater in term (n=12) vs. preterm (n=15) HUVECs (p=0.003). However, consistent with the immunohistochemistry in rats, the concentration of ICAM-1 was similar. Although defects in neonatal PMNs have been reported, the delayed expression of certain EC adhesion molecules may contribute to the delay in PMN transmigration in preterm human newborns.
