P-Selectin Expression by Endothelial Cells Is Decreased in Neonatal Rats and Human Premature Infants

Abstract

Decreased adhesion of neutrophils to endothelial cells and delayed transendothelial cell migration of neutrophils have been consistently reported in neonatal animals and humans and contribute to their susceptibility to infection. The delayed transmigration of neutrophils is especially prevalent in premature neonates. To define the nature of this defect, we used an in vivo animal model of inflammation and found that radiolabeled leukocytes from adult rats transmigrated into the peritoneum of other adult rats 5 times more efficiently than they did in neonatal rats (P = .05). This indicated that defects in neonatal neutrophils could not completely account for the delayed transmigration. Delayed transmigration in the neonatal rats correlated with a defect in the expression of P-selectin on the surface of their endothelial cells. We found a similar P-selectin deficiency in endothelial cells lining mesenteric venules and umbilical veins of human premature infants when compared with term human infants. The decreased P-selectin in premature infants was associated with decreased numbers of P-selectin storage granules and decreased P-selectin transcription. Decreased P-selectin expression on the surface of endothelial cells in preterm infants may contribute to delayed neutrophil transmigration and increased susceptibility to infection.

Inflammation in adult and neonatal stroke

“…Developmental differences in E-and P-selectin may underlie the disparities observed in post-ischemic neutrophil infiltration between adult and immature brain. While some studies have shown similar levels of E-and P-selectin in immature and adults rats [92], lower surface expression of P-selectin on endothelial cells or less efficient adhesion of neonatal neutrophils to P-selectin have been described by others [93,94] thus leaving open the question on whether selectins are accountable for the minimal in leukocyte transmigration through the BBB.…”

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

“…Although the HUC is formed during the fifth week of gestation, the bioenergetic capacity and immune response of HUVEC, obtained from preterm (<37 weeks of gestation) and full-term infants (37-40 weeks of gestation), are different [60][61][62][63][64]. HUVEC, obtained from preterm infants, show an impaired mitochondrial bioenergy capacity, and increased production of reactive oxygen species (ROS) [64].…”

“…Illsinger et al demonstrated that HUVEC mitochondrial enzyme activity changes lead to decreased viability of cells obtained from preterm cords [62]. In addition, the expression of selectins is lower in preterm HUVEC as compared to full-term HUVEC [60,61,63]. All these alterations affect endothelial function [60][61][62][63][64].…”

“…In addition, the expression of selectins is lower in preterm HUVEC as compared to full-term HUVEC [60,61,63]. All these alterations affect endothelial function [60][61][62][63][64]. Therefore, it is not recommended to use HUVEC obtained from preterm infants for the study of CVD.…”

Immunological peculiarities of extremely preterm infants: a challenge for the prevention of nosocomial sepsis

“…As principais moléculas envolvidas nestas interações são a selectina plaquetária (P-selectina), a selectina endotelial (E-seletina) e a selectina leucocitária (L-selectina) 16 . A P-selectina das plaquetas e células endoteliais é expressa de forma bastante tênue pelo endotélio fetal antes da 27ª semana de gestação, e sua expressão é praticamente normal no recém-nascido a termo e diminuída no recém-nascido pré-termo 22 . A L-selectina é expressa essencialmente nos leucócitos, havendo baixos níveis no cordão de recém-nascidos, principalmente em recém-nascidos pré-termo 23,24 .…”