LTB4 induced activation signals and responses in neutrophils are short-lived compared to formylpeptide.
Leukotriene B4 (LTB4) was shown to be a potent stimulator of neutrophil actin polymerization as detected by right-angle light scatter and rhodamine-phalloidin staining of F-actin. When we compared the kinetics of this neutrophil cytoskeletal response to the chemoattractants formylpeptide and LTB4, we observed that the response to LTB4 was markedly shorter-lived. To understand the basis of this result, we re-examined the kinetics of superoxide generation, elastase release, intracellular calcium elevation, and phosphoinositide metabolism in neutrophils stimulated with LTB4 and N-formylhexapeptide. LTB4 was relatively inefficient in producing superoxide and in releasing elastase. Although both responses were initiated with similar rapidity, they turned off sooner with LTB4 as compared with N-formylhexapeptide stimulation. Intracellular calcium elevation, a signal that is necessary for superoxide generation and degranulation, was of similar magnitude but of shorter duration in response to LTB4 as compared with the N-formylhexapeptide. The LTB4-induced rise of phosphatidic acid also was not sustained as long as the N-formylhexapeptide-induced increase. Prior exposure of neutrophils to LTB4 did not inhibit subsequent stimulation of superoxide generation by N-formylhexapeptide. Thus, the inability of LTB4 to stimulate superoxide generation was not due to LTB4-induced global inhibitory signals. The deficiency in LTB4-induced superoxide and elastase responses may be related to short-lived LTB4-induced activation signals and/or the number of receptors contributing to these responses.
D000199:Actins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D018102:Receptors, Leukotriene B4; D013481:Superoxides / Q000378:metabolism
D000199:Actins; D009842:Oligopeptides; D010716:Phosphatidylinositols; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D013481:Superoxides; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; C021642:F-chemotactic peptide; D010196:Pancreatic Elastase; D002118:Calcium