Comparative differences and combined effects of interleukin-8, leukotriene B4, and platelet-activating factor on neutrophil chemotaxis of the newborn.
IL-8, leukotriene B4 (LTB4), and platelet-activating factor (PAF) are potent neutrophil chemoattractants that have been identified in inflammatory conditions of the newborn such as chronic lung disease of extreme prematurity. The aims of this study were to determine the relative potency and combined effects of these mediators on chemotaxis of polymorphonuclear leukocytes (PMN) from the newborn and to compare the effect of combining all three mediators on chemotaxis of PMN from newborns and adults. Neutrophils were isolated from cord blood (n = 17) or healthy adults (n = 4) and incubated in a 3-tier, 48-well chemotaxis chamber. For PMN from newborns, using chemoattractant concentrations ranging from 0.01 to 100 nM, we found that there were significant differences in potency: IL-8 > LTB4 > PAF. Migration to each of these mediators was almost completely due to chemotaxis as opposed to chemokinesis. At submaximal chemotaxis, using equally effective doses of IL-8 (0.2 nM), LTB4 (1.0 nM), and PAF (10 nM), the combination of all three mediators increased chemotaxis 2.4-fold above the average individual responses. Further studies indicated this increase in chemotaxis was due to the combination of IL-8 and PAF or IL-8 and LTB4; but there was no increase in chemotaxis when PAF and LTB4 were combined. The combination of all three submaximal doses of chemoattractants resulted in PMN chemotaxis that was still 36% of the adult response.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D016209:Interleukin-8 / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012016:Reference Values
D016209:Interleukin-8; D010972:Platelet Activating Factor; D007975:Leukotriene B4