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.
D000199:Actins / Q000097:blood*; D000328:Adult; D002118:Calcium / Q000097:blood; D002634:Chemotaxis, Leukocyte; D005312:Fetal Blood; D005456:Fluorescent Dyes; D006801:Humans; D007231:Infant, Newborn; D046911:Macromolecular Substances; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D000199:Actins; D005456:Fluorescent Dyes; D046911:Macromolecular Substances; D009240:N-Formylmethionine Leucyl-Phenylalanine; D014700:Verapamil; D002118:Calcium