Leukotriene B4 is a Potent and Stereospecific Stimulator of Neutrophil Chemotaxis and Adherence

• Published in: Blood 1981-09, Vol.58 (3), p.658-661
• Main Authors: Palmblad, Jan, Malmsten, Curt L., Udén, Ann-Mari, Rådmark, Olof, Engstedt, Lars, Samuelsson, Bengt
• Format: Article
• Language: English
• Subjects: 5,8,11,14-Eicosatetraynoic Acid - pharmacology; Arachidonic Acids - pharmacology; Cell Adhesion - drug effects; Chemotaxis, Leukocyte - drug effects; Humans; Hydroxyeicosatetraenoic Acids; Indomethacin - pharmacology; Isomerism; Leukotriene B4; Luminescent Measurements; Neutrophils - drug effects; SRS-A - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V58.3.658.658

We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN) granulocytes. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10−6M, whereas two nonenzymatically formed isomers (compounds I and II) induced this response at 10−5M. Leukotriene C4 (LTC4) and 5-hydroxyeicosatetraenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with formyl-Met-Leu-Phe (fMLP) at 10−7M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aureus. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 × 10−7M, suggesting that arachidonic acid was then mainly metabolized by the lipoxygenase pathways. The lipoxygenase and cyclooxygenase inhibitor, eicosatetraynoic acid, inhibited both spontaneous and stimulated migration at ≥2.5 × 10−5M, but not at lower concentrations. Thus, since LTB4, and to a lesser degree compounds I and II, stimulated migration and adhesion, it is suggested that these mediators could be of importance for the emigration of neutrophils from blood vessels to areas of inflammation.