Comparison of leukotriene B4 and D4 effects on human eosinophil and neutrophil motility in vitro.
The motility of isolated normal human peripheral blood eosinophils and neutrophils in response to exogenous leukotrienes B4 and D4 was examined by means of a modified under-agarose technique and a novel quantitative sampling strategy. Leukotriene D4 was a potent chemoattractant for eosinophils, with a significant threshold chemotactic effect evident at 10(-10) M. The abolition of eosinophil chemotaxis by the potent and selective peptide-leukotriene-antagonist SK&F 104353 indicated the pharmacological specificity of the leukotriene D4-induced response. The chemokinetic response of eosinophils to leukotriene D4 generally did not differ significantly from spontaneous migratory activity of unstimulated cells. Leukotriene D4 did not, however, alter directed neutrophil motility until a very high concentration (10(-5) M) was achieved, although significant neutrophil chemokinesis relative to unstimulated movement was observed over the tested concentration range. Directional emigration of both eosinophils and neutrophils was induced by leukotriene B4 at concentrations as low as 10(-8) M. Analysis of leukocyte orientations provided evidence that chemokinetic responses were not being interpreted as indications of chemotactic behavior. These studies suggest that leukotriene D4 may behave as a potent and selective chemoattractant for human eosinophils at physiologically relevant concentrations.
Spada
C S
CS
Department of Biological Sciences, Allergan, Inc., Irvine, California.
Nieves
A L
AL
Krauss
A H
AH
Woodward
D F
DF
D002448:Cell Adhesion; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013189:SRS-A / Q000037:antagonists & inhibitors
D003998:Dicarboxylic Acids; D013189:SRS-A; D007975:Leukotriene B4; D017998:Leukotriene D4; C052393:pobilukast