Heterogeneity of human mast cells and basophils. Effects of a putative 5-lipoxygenase inhibitor.
The effects of a putatively specific 5-lipoxygenase inhibitor, 2(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoquin one (AA-861), and its major metabolite, M-I, were assessed using anti-IgE activated human basophils, lung mast cells and skin mast cells. In basophils and lung mast cells, no effects on histamine release were observed, whereas leukotriene C4 (LTC4) production was inhibited (IC50 values less than 1 microM). In addition, prostaglandin D2 (PGD2) production was inhibited in lung mast cells (IC50 congruent to 5 microM). In contrast, in skin mast cells both histamine release and PGD2 production were reduced by AA-861 and M-I, with IC50 values of congruent to 5 and 0.4 microM for histamine and PGD2, respectively. These data reveal biochemical heterogeneity among human histamine-containing cells and underscore the necessity of assessing a pharmacologic agonist in relevant cell systems.
Cohan
V
V
Division of Clinical Immunology, Johns Hopkins University School of Medicine, Good Samaritan Hospital, Baltimore, MD 21239.
McKenzie-White
J
J
Triggiani
M
M
Massey
W
W
Kagey-Sobotka
A
A
Lichtenstein
L M
LM
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D001491:Basophils / Q000378:metabolism; D016227:Benzoquinones; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008084:Lipoxygenase / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D008407:Mast Cells / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors; D011809:Quinones; D013189:SRS-A; D007073:Immunoglobulin E; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase