Differential neutrophil chemotactic response towards IL-8 and bacterial N-formyl peptides in term newborn infants

Abstract

BackgroundA prerequisite for an effective innate immunity is the migrative ability of neutrophils to respond to inflammatory and infectious agents such as the intermediate interleukin (IL)-8 and the end-target formyl-methionyl-leucyl-phenylalanine (fMLP) chemoattractants. The aim was to study the chemotactic capacity of neutrophils from newborn infants and adults in response to IL-8 and the bacterial peptide fMLP.MethodsIn the under-agarose cell migration assay, isolated leukocytes from healthy adults and from cord blood of healthy term newborn infants were studied with dose responses towards IL-8 and fMLP. The same number of leukocytes (1 × 105 cells), with the same distribution of neutrophils and monocytes, were analyzed in neonates and adults. Chemotaxis was distinguished from randomly migrating neutrophils, and the neutrophil pattern of migration, i.e. the migration distance and the number of migrating neutrophils per distance, was evaluated.ResultsIn comparison to adults, fewer neutrophils from newborn infants migrated towards IL-8 and for a shorter distance (P < .01, respectively). The number of neutrophils migrating to different gradients of fMLP, the distance they migrated, and the correlation between the number and the distance were the same for neonates and adults. Random migration did not differ in any instance.ConclusionChemotaxis of neutrophils from newborn infants was as co-ordinated as neutrophils from adults in response to fMLP, whereas the response to IL-8 was reduced. The differential response of neutrophils from neonates to intermediate and end-target chemoattractants could indicate a reduced infectious response.

Neutrophil Receptor Response to Bacterial N‐formyl Peptides is Similar in Term Newborn Infants and Adults in Contrast to IL‐8

“…In the present study, CD44 receptors in resting neutrophils from neonates were also fewer than in adults, a finding not previously described. As CD44 plays an essential role for migrating neutrophils, the reduced number of receptors could contribute to the reduced migration in response to IL‐8 observed in our previous study . Similar to other studies, the expression of CD64 on resting neutrophils from neonates was higher than in adults (Table ) .…”

“…Our observation that the response to intermediate chemoattractants is compromised in newborn infants is supported by Urlichs et al [18]. In a previous study, we observed that IL-8 induced a markedly lower chemotactic response in neutrophils from newborns than from adults in terms of the amount of chemotactic cells and the distance of migration [2]. On the other hand, the same neutrophil receptor expression changes were observed in neonates and adults in response to fMLP, for all the receptors involved in adhesion, chemotaxis, granula activation and phagocytosis (Table 3b).…”

“…Because of a reduced neutrophil influx at the site of infection in newborn infants, increased bacterial growth may lead to a rapidly progressive infection which in turn could deplete the limited bone marrow neutrophil pool in neonates [26]. The compromised response towards IL-8 previously observed in newborn infants in terms of reduced migration [2] was supported by the reduced modulation of receptors involved in adhesion and chemotaxis, in neutrophils from newborn infants as compared to adults. On the other hand, we observed similar modulation of receptors involved in adhesion, migration, granula activation and phagocytosis in response to fMLP on neutrophils from neonates and adults.…”

“…On the other hand, the same neutrophil receptor expression changes were observed in neonates and adults in response to fMLP, for all the receptors involved in adhesion, chemotaxis, granula activation and phagocytosis (Table b). This confirms the normal response of neutrophils from newborn infants to end‐target chemoattractants produced by bacteria, observed in one of our previous studies and also by Birle et al ., with equivalent neutrophil chemotactic capacity. In addition, similar numbers and affinity of receptors for fMLP in neutrophils from neonates and adults have been observed previously .…”

“…Neutrophil activation is part of the innate immunity and the most important immune defence against invading microbes in newborn infants. We have previously observed that the neutrophil chemotactic response towards formyl-methionyl-leucyl-phenylalanine (fMLP) was of similar magnitude in neonates as in adults, whereas the response to IL-8 was reduced in neonates [2]. This indicates that neutrophils from neonates display different responses to end-target and intermediate chemoattractants, which could result in a compromised infectious response.…”