Diminished actin polymerization by neutrophils from newborn infants.
During the newborn period, abnormalities of neutrophil (PMN) function predispose infants to serious bacterial disease. Actin is a major contributor to PMN shape change and motile behavior. To determine the mechanism underlying defects in newborn granulocyte polarity and chemotaxis, we investigated actin polymerization by cord blood PMN from healthy term infants and adult controls. F-actin (filamentous) content was quantified in the resting state and after stimulation by fluorescence-activated cell-sorter analysis of nitrobenzoxadiazole-phallacidin-stained cells. PMN from newborn infants demonstrated similar basal F-actin levels when compared with adults. N-formyl methionyl leucyl phenylalanine induced a marked increase in actin polymerization that was maximal at 30 s in both neonates and adults and that then declined slowly (depolymerization) over the following 10 min. However, the F-actin content of PMN from newborn infants was significantly diminished when compared with adults at 30 and 60 s after N-formyl methionyl leucyl phenylalanine stimulation (p < 0.05). Both the rate and dose response of N-formyl methionyl leucyl phenylalanine-induced actin polymerization were similar for adult and neonatal PMN. PMN from newborn infants also demonstrated significantly diminished actin polymerization when compared with adults 60 s after stimulation with platelet-activating factor (p < 0.05). Decreased concentrations of F-actin may help explain the observed abnormalities of PMN polarity and chemotaxis in healthy newborn infants.
Harris
M C
MC
Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia.
Shalit
M
M
Southwick
F S
FS
D000199:Actins / Q000097:blood*; D000328:Adult; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism
D000199:Actins; D010972:Platelet Activating Factor; D011108:Polymers; D009240:N-Formylmethionine Leucyl-Phenylalanine