Modulation of human monocyte leukotactic responsiveness by thromboxane A2 and 12-hydroxyheptadecatrienoic acid (12-HHT).
The leukotactic responsiveness of human peripheral blood monocytes is regulated by the cell-directed inhibitor of monocyte leukotaxis, CDI-MLx. The actions of CDI-MLx on normal monocytes in vitro were abrogated by co-incubation with inhibitors of cyclooxygenase and thromboxane synthetase with indomethacin and dazmegrel (UK-38,485) being most active. The actions of CDI-MLx were mimicked by the thromboxane A2 analogue, U-46619, and by 12-HHT with half-maximal inhibition observed at 10(-10) M; PGE2 was 1000-fold less active. SQ 29,548, a thromboxane A2 receptor antagonist, blocked the effects of CDI-MLx, U-46619, and 12-HHT. Production of PGE2 and thromboxane B2 by purified monocytes was stimulated by CDI-MLx and this effect was also blocked by indomethacin, dazmegrel, and dazoxiben. These data suggest a major regulatory role for thromboxane synthetase products in human monocyte leukotaxis.
Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354.
P B
PB
Campbell
T A
TA
Tolson
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015232:Dinoprostone; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008222:Lymphokines / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011458:Prostaglandins E / Q000032:analysis; D011863:Radioimmunoassay; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002630:Chemotactic Factors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008222:Lymphokines; D011450:Prostaglandin Endoperoxides, Synthetic; D011458:Prostaglandins E; C034397:chemotactic inhibitory factor; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013928:Thromboxane A2; C045749:SQ 29548; D015232:Dinoprostone