Induction of vascular injury by Pseudomonas aeruginosa cytotoxin in rabbit lungs is associated with the generation of different leukotrienes and hydroxyeicosatetraenoic acids.
Pseudomonas aeruginosa cytotoxin, a transmembrane pore-forming protein, causes an increase in pulmonary microvascular permeability with subsequent lung edema formation, possibly related to the induction of arachidonic acid (AA) lipoxygenase products. To investigate this, isolated rabbit lungs were perfused with cytotoxin-containing buffer (6.5 and 13 micrograms of toxin/ml). A severalfold increase in the capillary filtration coefficient was induced, both preceded and accompanied by a marked time- (15-60 min) and dose-dependent release of cysteinyl leukotrienes (LT), LTB4, and 5-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs) into the lung perfusate. In the bronchoalveolar lavage fluid, corresponding AA-derived products were detected; the total sum of HETEs surpassed that of cysteinyl LTs in this compartment. The lipoxygenase inhibitors AA861 (10 microM) and nordihydroguaiaretic acid (100 microM) and EGTA (5 mM) suppressed the intravascular and alveolar liberation of all 5-lipoxygenase-derived AA metabolites, paralleled by a marked reduction and retardation of microvascular permeability increase (AA861). It thus seems that Pseudomonas cytotoxin induces generation of LTs and HETEs in rabbit lungs that may contribute to the development of pulmonary microvascular injury evoked by this bacterial agent.
Grimminger
F
F
Department of Internal Medicine, Justus-Liebig University, Giessen, Federal Republic of Germany.
Walmrath
D
D
Walter
H
H
Lutz
F
F
Seeger
W
W
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D002851:Chromatography, High Pressure Liquid; D003603:Cytotoxins / Q000633:toxicity*; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D015289:Leukotrienes / Q000096:biosynthesis*; D008168:Lung / Q000098:blood supply*; D008297:Male; D009924:Organ Culture Techniques; D011550:Pseudomonas aeruginosa; D011817:Rabbits
D003603:Cytotoxins; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes