Suppression of leukotriene synthesis in human leukocytes by a urea extract of Bordetella pertussis: evidence for mediation by adenylate cyclase toxin.
Incubation of human leukocytes with a urea extract of Bordetella pertussis led to inhibition of zymosan-induced leukotriene generation. The proteins in this extract are known to include an adenylate cyclase which suppresses certain defense mechanisms of leukocytes against bacterial invasion. The formation of leukotriene B4 and leukotriene C4, induced by serum-coated zymosan, was almost completely inhibited in the presence of 75 micrograms of urea-extracted proteins/ml cell suspension. This suppression by the bacterial urea extract was rapid, with the maximum effect occurring in the first min of incubation. The reduction in leukotriene generation was accompanied by a dramatic increase in intracellular cyclic AMP levels. Since leukotrienes are potent pro-inflammatory compounds, the present study indicates that Bordetella pertussis-induced suppression of leukotriene formation might be an important factor in the increased susceptibility to secondary bacterial infection, which occurs as a result of this disease.
Green
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FA
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Gustafsson
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B
Claesson
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HE
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D015289:Leukotrienes / Q000096:biosynthesis*; D014508:Urea; D010566:Virulence Factors, Bordetella / Q000633:toxicity*
D037361:Adenylate Cyclase Toxin; D015289:Leukotrienes; D010566:Virulence Factors, Bordetella; D014508:Urea; D000242:Cyclic AMP; D000262:Adenylyl Cyclases