Title: Neutrophil Chemotaxis to Leukotriene B4 In Vitro is Decreased for the Human Neonate
Abstract: ABSTRACT: Leukotriene B4 (LTB4) is a product of arachidonic acid metabolism and a potent chemoattractant for adult polymorphonuclear leukocytes (PMN). LTB4 may be an important inflammatory mediator in neonatal lung disorders such as bronchopulmonary dysplasia, but neonatal PMN chemotaxis to LTB4 has not been studied. We compared total PMN migration and its components, chemotaxis and chemokinesis, to LTB4 in newborns and adults. PMN from healthy adults and umbilical blood of healthy, full-term newborns (n = 21 pairs) were incubated in a 48-well chemotaxis chamber using 10-μm thick polycarbonate membranes. Membranes with pore sizes of either 3 or 5 μm (diameter) were used to assess the influence of PMN deformability on chemotaxis. For both 3− and 5-μm filter pore sizes, total PMN migration increased in a dose-dependent manner from an LTB4 concentration of 10-9 to 10-6 M. The increase in total PMN migration was due entirely to chemotaxis (no chemokinesis) for newborns and adults. However, chemotaxis for the newborn was markedly attenuated, specifically, 14 and 24% of adult values at LTB4 concentrations of 10-8 and 10-7 M, respectively, with the 3-μm pore size. With the 5-μm filter pore size, newborn chemotaxis significantly increased to 40 and 49% of adult values at LTB4 concentrations of 10-8 and 10-7 M, respectively. We conclude that PMN chemotaxis to LTB4 in vitro is lower in newborns than in adults and part of this impairment may be caused by a decreased deformability of the newborn PMN. Decreased PMN chemotaxis to LTB4 may protect against excessive inflammation, as in bronchopulmonary dysplasia, but may increase susceptibility to infection in the newborn.