Lipoxin A4 inhibits phosphoinositide hydrolysis in human neutrophils.
Lipoxins (LX) are trihydroxytetraene metabolites derived from arachidonic acid via an interaction between the 5- and 15-lipoxygenases. Preincubation of [3H] myo-inositol labeled PMN with 10-7M and 10-5M LXA4 for 1 minute at 37 degrees C resulted in a concentration dependent inhibition of the generation of [3H] IP3 and [3H] IP in cells subsequently stimulated by increasing doses of LTB4 or FMLP for 1 minute at 37 degrees C. Preincubation of PMN with LXA4 did not inhibit specific binding of [3H] LTB4 to PMN. These results indicate that LXA4 inhibits chemotactic factor-induced phosphoinositide hydrolysis at a post-receptor level.
Grandordy
B M
BM
Department of Allergy and Allied Respiratory Disorders, U.M.D.S., Guy's Hospital, London, U.K.
Lacroix
H
H
Mavoungou
E
E
Krilis
S
S
Crea
A E
AE
Spur
B W
BW
Lee
T H
TH
D004305:Dose-Response Relationship, Drug; D006801:Humans; D006868:Hydrolysis; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007294:Inositol / Q000097:blood; D015544:Inositol 1,4,5-Trisphosphate / Q000097:blood; D007295:Inositol Phosphates / Q000097:blood; D007700:Kinetics; D007975:Leukotriene B4 / Q000097:blood / Q000494:pharmacology; D044045:Lipoxins; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000097:blood*
D006893:Hydroxyeicosatetraenoic Acids; D007295:Inositol Phosphates; D044045:Lipoxins; D010716:Phosphatidylinositols; C040527:lipoxin A4; D007975:Leukotriene B4; D007294:Inositol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate