The effect of 20-trifluoromethyl leukotriene B4 on neutrophil functional responses.
20-trifluoromethyl-leukotriene B4 (20CF3-LTB4) is a stable derivative of leukotriene B4 (LTB4) that is not subjected to omega-oxidation to less active metabolites. 20CF3-LTB4 was as potent as LTB4 as a chemotactic, adhesion-promoting and aggregatory agent for human neutrophils, but had only 11 +/- 3% of the ability to induce an oxidative response. Nonetheless, both compounds were equally efficient in order to confer a rapid and monophasic increment of the concentration of cytosolic calcium. The kinetics of the calcium, aggregatory and chemiluminescent responses to 20CF3-LTB4 were similar to that of LTB4. These findings suggest that the insertion of the trifluoromethyl group into the LTB4 molecule causes a shift of the biological activity profile, suggesting that 20CF3-LTB4 binds mainly to high affinity LTB4 receptors. Moreover, the similarity of the response kinetics of LTB4 and 20CF3-LTB4 suggests that the mechanism for the rapid and transient responses of LTB4 is not due to its omega-oxidation.
Nilsson
E
E
Department of Medicine, Karolinska Institute at Södersjukhuset, Stockholm, Sweden.
Gyllenhammar
H
H
Lerner
R
R
Palmblad
J
J
Ringertz
B
B
D002118:Calcium / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology* / Q000031:analogs & derivatives; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects*
C059892:20-trifluoromethylleukotriene B4; D007975:Leukotriene B4; D002118:Calcium