Effects of two leukotriene B4 (LTB4) receptor antagonists (LY255283 and SC-41930) on LTB4-induced human neutrophil adhesion and superoxide production.
Leukotriene B4 (LTB4) induces a number of functional changes in human neutrophils, including both superoxide release and CD11b/CD18 (Mo1)-mediated adherence to various substrates, such as keyhole limpet hemocyanin (KLH). These effects are both time- and concentration-dependent. Neutrophil adhesion was at least 10-fold more sensitive to the stimulatory action of LTB4 than superoxide production. Two LTB4 receptor antagonists, LY255283 (1-(5-ethyl-2-hydroxy-4-(6-methyl-6-(1H-tetrazol-5-yl)heptyloxy )- phenyl)ethanone) and the sodium salt of SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl-2H- 1-benzopyran-2-carboxylic acid) were evaluated for effects on human neutrophil superoxide production and adhesion. Despite being more sensitive to LTB4-induced stimulation, neutrophil adhesion was at least 100-fold less sensitive to inhibition by LY255283 and SC-41930 than superoxide production. Both LTB4 receptor antagonists behaved similarly in these models. These compounds did not inhibit neutrophil responses induced by granulocyte/macrophage colony-stimulating factor (GM-CSF).
Schultz
R M
RM
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
Marder
P
P
Spaethe
S M
SM
Herron
D K
DK
Sofia
M J
MJ
D000328:Adult; D001578:Benzopyrans / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000097:blood / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018102:Receptors, Leukotriene B4; D013481:Superoxides / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology
D001578:Benzopyrans; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D013777:Tetrazoles; D013481:Superoxides; C059950:SC 41930; D007975:Leukotriene B4; C063823:LY 255283