Abstract
BackgroundInsufficient leukocyte recruitment may be one reason for the high incidence of life-threatening infections in preterm infants. Since the receptor of advanced glycation end products (RAGE) is a known leukocyte adhesion molecule and highly expressed during early development, we asked whether RAGE plays a role for leukocyte recruitment in preterm and term infants.MethodsLeukocyte adhesion was analyzed in dynamic flow chamber experiments using isolated leukocytes of cord blood from extremely premature (<30 weeks of gestation), moderately premature (30–35 weeks of gestation) and mature neonates (>35 weeks of gestation) and compared to the results of adults. For fluorescent microscopy leukocytes were labeled with rhodamine 6G. In the respective age groups we also measured the plasma concentration of soluble RAGE (sRAGE) by ELISA and Mac-1 and LFA-1 expression on neutrophils by flow cytometry.ResultsThe adhesive functions of fetal leukocytes significantly increase with gestational age. In all age groups, leukocyte adhesion was crucially dependent on RAGE. In particular, RAGE was equally effective to mediate leukocyte adhesion when compared to ICAM-1. The plasma levels of sRAGE were high in extremely premature infants and decreased with increasing gestational age. In contrast, expression of β2-Integrins Mac-1 and LFA-1 which are known ligands for RAGE and ICAM-1 did not change during fetal development.ConclusionWe conclude that RAGE is a crucial leukocyte adhesion molecule in both preterm and term infants.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-014-0053-0) contains supplementary material, which is available to authorized users.
Highlights
Insufficient leukocyte recruitment may be one reason for the high incidence of life-threatening infections in preterm infants
With regard to our flow chamber results we argue that the role of receptor of advanced glycation end products (RAGE)-dependent leukocyte adhesion may be more prominent during early development than during later life
Leukocyte functional antigen-1 (LFA-1) and Macrophage antigen complex 1 (Mac-1) expression during fetal development We investigated the age-dependent expression of the β2-integrins LFA-1 and Mac-1 which are known to be relevant receptors of Intercellular adhesion molecule-1 (ICAM-1) and RAGE
Summary
Insufficient leukocyte recruitment may be one reason for the high incidence of life-threatening infections in preterm infants. Since the receptor of advanced glycation end products (RAGE) is a known leukocyte adhesion molecule and highly expressed during early development, we asked whether RAGE plays a role for leukocyte recruitment in preterm and term infants. Especially among very immature infants, infection and sepsis are still the leading causes for mortality and morbidity [2,3,4]. As immaturity of the innate immune system seems to be one of the reasons for this observation, the role of leukocytes has been addressed by numerous studies [2,3,4,5]. The cascade of leukocyte recruitment plays a crucial role in the immune defense during inflammation [9]. Capture of free flowing leukocytes is followed by leukocyte rolling along the endothelial layer, triggering the activation of β2-
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