Leukotriene B4 stimulates human monocyte-derived dendritic cell chemotaxis.
Although leukotriene B4 (LTB4) has been reported to stimulate monocytes and neutrophils, its role on dendritic cell (DC) activity has not been examined. Here, we investigated the expression of LTB4 receptor and the effect of LTB4 on human DC chemotaxis. We analyzed LTB4 receptors, BLT1 and BLT2, by using RT-PCR. DCs express BLT2 but not BLT1 mRNA. DCs were chemotactically migrated to LTB4. LTB4-induced DC chemotaxis was completely inhibited by pertussis toxin, indicating the role of Gi proteins. LTB4 induced mitogen activated protein kinase activation and Akt activation. LTB4-induced DC chemotaxis was mediated by extracellular signal-regulated protein kinase and phosphoinositide 3-kinase but not by p38 kinase. BLT2-selevite antagonist, LY255283, almost completely inhibited DC chemotaxis induced by LTB4 but not by Trp-Lys-Tyr-Met-Val-D-Met. Thus human myeloid DCs express functional BLT2 but not BLT1, suggesting a physiological role of LTB4 and BLT2 in regulating DC trafficking during induction of immune responses.
Shin
Eun Ha
EH
Medical Research Center for Cancer Molecular Therapy and Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Lee
Ha Young
HY
Bae
Yoe-Sik
YS
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology*; D009000:Monocytes; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
C513240:LTB4R protein, human; C485878:LTB4R2 protein, human; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D013777:Tetrazoles; D007975:Leukotriene B4; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019204:GTP-Binding Proteins; C063823:LY 255283; D002118:Calcium