Fulvio Sacchi

Different maturation of neutrophil chemotaxis in term and preterm newborn infants

N EW BORN I N FAN TS are known to be particularly susceptible to bacterial infections1-2; the preterm infant is even more susceptible than the term neonate? Impairment of neutrophil functions (chemotaxis, chemolumineseence production, hexose monophosphate shunt activity, and intracellular microbicidal activity) has been found in healthy and stressed newborn infants and related to the susceptibility to infections in these subjects. .6 Miller 4 has suggested that defective neutrophil chemotaxis is one of the main causes of frequent neonatal infections, and this finding has been confirmed by in vivo data. 7 Laurenti et al s have reported that the defect of chemotaxis in preterm infants is similar to that in normal neonates. Up to now, however, only cross-sectional data are available and no longitudinal Studies have been Carried out. The purpose of the present study was to establish the duration of the defect in term and preterm infants.

Abnormality in Actin Polymerization Associated with Defective Chemotaxis in Neutrophils from Neonates

In an attempt to determine the mechanism of the profound defect in chemotaxis observed in the neutrophils of human neonates, we have examined the generation of polymerized or filamentous actin (F actin) following stimulation of the cells with chemotactic factors. We have also examined the changes in the intracellular levels of free calcium in neonatal neutrophils and compared the results with those in adult neutrophils. Following exposure to formyl-methionyl-leucyl-phenylalanine (FMLP) or zymosan-activated serum (ZyAS), neutrophils from adult donors showed an increase in intracellular free calcium, as determined by Quin 2/AM fluorescence, and in actin polymerization (45-55%), as measured by nitrobenzoxadiazole phallicidin fluorescence. These responses were abolished by preincubation with the calcium antagonist verapamil (0.1 mM), which inhibits both calcium influx and release from intracellular stores. In marked contrast to the results obtained with neutrophils from adults, neutrophils from newborn infants, which have defective chemotactic responses, failed to generate F actin following FMLP or ZyAS stimulation and developed significantly lower levels of free intracellular calcium.

A defect in neutrophil motility in two siblings with recurrent infections and a remarkable family history.

SummaryTwo siblings with recurrent infections were found to have impaired neutrophil motility. The same association of infections (otitis media, bronchitis, chronic diarrhoea) has caused seven fatalities in the paternal side of the family, suggesting genetic implications.ZusammenfassungBei zwei Geschweistern mit wiederholten Infektionen ist ein wahrscheinlich genetischer Schaden der Granulocyten-Chemotaxis gefunden worden. Durch Häufung von Infekten (Mittelohrentzündung, Bronchitis, chronischer Durchfall) sind sieben Geschwister in der väterlichen Familie in jungem Alter gestorben.

Effects of Aminoglycoside Antibiotics on Neutrophil Chemotaxis

The inhibitory effect of neutrophil chemotaxis of gentamicin, tobramycin, and sisomicin was shown. The combined effect of aminoglycosides and histamine was not additive.

Mechanisms of Abnormal Neutrophil Function in the Human Neonate: Prospects for Therapy

Human neonates have an increased incidence of infections when compared with older children and adults (Hill 1985; Santos and Hill 1982; Klein and Marcy 1983). The infections suffered by term and especially premature infants are usually due to bacterial and fungal agents that may not be particularly virulent in older individuals unless they are immunocompromised. These include pathogens such as group B streptococci, Staphylococcus epidermidis, Listeria monocytogenes, Escherichia coli and Candida albicans (Santos and Hill 1982; Klein and Marcy 1983). Furthermore, newborns often develop infections in peripheral sites, such as on the skin, in subcutaneous tissues, or in the lungs. Phagocytic cells, including polymorphonuclear leukocytes and macrophages, are critical to the defense of these areas. Miles et al. (1957) have shown, in experimental animals, that phagocytic cells must arrive at a site of microbial invasion, ingest the pathogen, and kill it within a critical 2-4 h period. If this does not occur, the animal will eventually develop a larger local or systemic infection.

Use and Results of Neutrophil Function Testing in Pediatric Immunology

A working group (Table 1) has been set up in Pavia to evaluate the relevance of neutrophil function in patients suffering from recurrent infections.