Arachidonic acid-induced mobilization of calcium in human neutrophils: evidence for a multicomponent mechanism of action.
1. The mechanism(s) involved in the mobilization of calcium induced by arachidonic acid in human neutrophils was investigated. 2. The addition of arachidonic acid to a suspension of human neutrophils led to a time- and concentration-dependent mobilization of calcium which was the result of two separate and experimentally differentiable processes. The latter consisted of a rapid and transient phase followed by a slower and more sustained response. 3. The initial phase of calcium mobilization elicited by arachidonic acid was decreased in the presence of EGTA, inhibited by pertussis toxin as well as by nordihydroguaiaretic acid (NDGA), and diminished following a pre-incubation with leukotriene B4, but not platelet-activating factor. 4. The characteristics of the first phase of the mobilization of calcium were consistent with an interaction of the fatty acid with the leukotriene B4 receptors, either directly or indirectly following the synthesis of leukotriene B4, as well as with a release of internal calcium. 5. The second, slower and more sustained phase of calcium mobilization was more apparent at high concentrations (greater than or equal to 8-16 microM) of arachidonic acid, and was relatively insensitive to pertussis toxin, EGTA or NDGA. 6. The characteristics of the 'slow' phase of calcium mobilization by arachidonic acid are consistent with its being associated primarily with a release of calcium from internal storage pools. 7. The data presented indicate that the mechanism of mobilization of calcium by arachidonic acid in human neutrophils is complex and involves specific activation pathways employed, in part at least, by other neutrophil agonists. These findings may have relevance to various inflammatory situations in which the elevated levels of extracellular arachidonic acid known to be present could modulate the functional responsiveness of the neutrophils to other stimuli.
Naccache
P H
PH
Unité de Recherche Inflammation et Immunologie-Rhumatologie, Centre Hospitalier de l'Université Laval, Ste Foy, Québec, Canada.
McColl
S R
SR
Caon
A C
AC
Borgeat
P
P
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D010566:Virulence Factors, Bordetella; D007975:Leukotriene B4; D016718:Arachidonic Acid; D004533:Egtazic Acid; D009637:Masoprocol; D002772:Cholera Toxin; D037342:Pertussis Toxin; D002118:Calcium